The potential for fungal biopesticides to reduce malaria transmission under diverse environmental conditions

The effectiveness of conventional malaria vector control is being threatened by the spread of insecticide resistance. One promising alternative to chemicals is the use of naturally occurring insect-killing fungi. Numerous laboratory studies have shown that isolates of fungal pathogens such as Beauveria bassiana can infect and kill adult mosquitoes, including those resistant to chemical insecticides. Unlike chemical insecticides, fungi may take up to a week or more to kill mosquitoes following exposure. This slow kill speed can still reduce malaria transmission because the malaria parasite itself takes at least eight days to complete its development within the mosquito. However, both fungal virulence and parasite development rate are strongly temperature-dependent, so it is possible that biopesticide efficacy could vary across different transmission environments. We examined the virulence of a candidate fungal isolate against two key malaria vectors at temperatures from 10 to 34 °C. Regardless of temperature, the fungus killed more than 90% of exposed mosquitoes within the predicted duration of the malarial extrinsic incubation period, a result that was robust to realistic diurnal temperature variation. We then incorporated temperature sensitivities of a suite of mosquito, parasite and fungus life-history traits that are important determinants of malaria transmission into a stage-structured malaria transmission model. The model predicted that, at achievable daily fungal infection rates, fungal biopesticides have the potential to deliver substantial reductions in the density of malaria-infectious mosquitoes across all temperatures representative of malaria transmission environments. Synthesis and applications. Our study combines empirical data and theoretical modelling to prospectively evaluate the potential of fungal biopesticides to control adult malaria vectors. Our results suggest that Beauveria bassiana could be a potent tool for malaria control and support further development of fungal biopesticides to manage infectious disease vectors

Implementation of a health care policy: An analysis of barriers and facilitators to practice change

BACKGROUND: Governments often create policies that rely on implementation by arms length organizations and require practice changes on the part of different segments of the health care system without understanding the differences in and complexities of these agencies. In 2000, in response to publicity about the shortening length of postpartum hospital stay, the Ontario government created a universal program offering up to a 60-hour postpartum stay and a public health follow-up to mothers and newborn infants. The purpose of this paper is to examine how a health policy initiative was implemented in two different parts of a health care system and to analyze the barriers and facilitators to achieving practice change. METHODS: The data reported came from two studies of postpartum health and service use in Ontario Canada. Data were collected from newly delivered mothers who had uncomplicated vaginal deliveries. The study samples were drawn from the same five purposefully selected hospitals for both studies. Questionnaires prior to discharge and structured telephone interviews at 4-weeks post discharge were used to collect data before and after policy implementation. Qualitative data were collected using focus groups with hospital and community-based health care practitioners and administrators at each site. RESULTS: In both studies, the respondents reflected a population of women who experienced an "average" or non-eventful hospital-based, singleton vaginal delivery. The findings of the second study demonstrated wide variance in implementation of the offer of a 60-hour stay among the sites and focus groups revealed that none of the hospitals acknowledged the 60-hour stay as an official policy. The uptake of the offer of a 60-hour stay was unrelated to the rate of offer. The percentage of women with a hospital stay of less than 25 hours and the number with the guideline that the call be within 48 hours of hospital discharge. Public health telephone contact was high although variable in relation to compliance the guideline that the call be within 48 hours of hospital discharge. Home visits were offered at consistently high rates. CONCLUSION: Policy enactment is sometimes inadequate to stimulate practice changes in health care. Policy as a tool for practice change must thoughtfully address the organizational, professional, and social contexts within which the policy is to be implemented. These contexts can either facilitate or block implementation. Our examination of Ontario's universal postpartum program provides an example of differential implementation of a common policy intended to change post-natal care practices that reflects the differential influence of context on implementation

First Observation of τ→3πηντ\tau\to 3\pi\eta\nu_{\tau} and τ→f1πντ\tau\to f_{1}\pi\nu_{\tau} Decays

We have observed new channels for $\tau$ decays with an $\eta$ in the final state. We study 3-prong tau decays, using the $\eta\to\gamma\gamma$ and \eta\to 3\piz decay modes and 1-prong decays with two \piz's using the $\eta\to\gamma\gamma$ channel. The measured branching fractions are \B(\tau^{-}\to \pi^{-}\pi^{-}\pi^{+}\eta\nu_{\tau}) =(3.4^{+0.6}_{-0.5}\pm0.6)\times10^{-4} and \B(\tau^{-}\to \pi^{-}2\piz\eta\nu_{\tau} =(1.4\pm0.6\pm0.3)\times10^{-4}. We observe clear evidence for $f_1\to\eta\pi\pi$ substructure and measure \B(\tau^{-}\to f_1\pi^{-}\nu_{\tau})=(5.8^{+1.4}_{-1.3}\pm1.8)\times10^{-4}. We have also searched for $\eta'(958)$ production and obtain 90% CL upper limits \B(\tau^{-}\to \pi^{-}\eta'\nu_\tau)<7.4\times10^{-5} and \B(\tau^{-}\to \pi^{-}\piz\eta'\nu_\tau)<8.0\times10^{-5}.Comment: 11 page postscript file, postscript file also available through http://w4.lns.cornell.edu/public/CLN

Search for the Decays B^0 -> D^{(*)+} D^{(*)-}

Using the CLEO-II data set we have searched for the Cabibbo-suppressed decays B^0 -> D^{(*)+} D^{(*)-}. For the decay B^0 -> D^{*+} D^{*-}, we observe one candidate signal event, with an expected background of 0.022 +/- 0.011 events. This yield corresponds to a branching fraction of Br(B^0 -> D^{*+} D^{*-}) = (5.3^{+7.1}_{-3.7}(stat) +/- 1.0(syst)) x 10^{-4} and an upper limit of Br(B^0 -> D^{*+} D^{*-}) D^{*\pm} D^\mp and B^0 -> D^+ D^-, no significant excess of signal above the expected background level is seen, and we calculate the 90% CL upper limits on the branching fractions to be Br(B^0 -> D^{*\pm} D^\mp) D^+ D^-) < 1.2 x 10^{-3}.Comment: 12 page postscript file also available through http://w4.lns.cornell.edu/public/CLNS, submitted to Physical Review Letter

Infection of the malaria mosquito, Anopheles gambiae, with two species of entomopathogenic fungi: effects of concentration, co-formulation, exposure time and persistence

<p>Abstract</p> <p>Background</p> <p>Entomopathogenic fungi <it>Metarhizium anisopliae </it>and <it>Beauveria bassiana </it>isolates have been shown to infect and reduce the survival of mosquito vectors.</p> <p>Methods</p> <p>Here four different bioassays were conducted to study the effect of conidia concentration, co-formulation, exposure time and persistence of the isolates <it>M. anisopliae </it>ICIPE-30 and <it>B. bassiana </it>I93-925 on infection and survival rates of female <it>Anopheles gambiae sensu stricto</it>. Test concentrations and exposure times ranged between 1 × 10⁷- 4 × 10¹⁰conidia m^-2and 15 min - 6 h. In co-formulations, 2 × 10¹⁰conidia m^-2of both fungus isolates were mixed at ratios of 4:1, 2:1, 1:1,1:0, 0:1, 1:2 and 1:4. To determine persistence, mosquitoes were exposed to surfaces treated 1, 14 or 28 d previously, with conidia concentrations of 2 × 10⁹, 2 × 10¹⁰or 4 × 10¹⁰.</p> <p>Results</p> <p>Mosquito survival varied with conidia concentration; 2 × 10¹⁰conidia m^-2was the concentration above which no further reductions in survival were detectable for both isolates of fungus. The survival of mosquitoes exposed to single and co-formulated treatments was similar and no synergistic or additive effects were observed. Mosquitoes were infected within 30 min and longer exposure times did not result in a more rapid killing effect. Fifteen min exposure still achieved considerable mortality rates (100% mortality by 14 d) of mosquitoes, but at lower speed than with 30 min exposure (100% mortality by 9 d). Conidia remained infective up to 28 d post-application but higher concentrations did not increase persistence.</p> <p>Conclusion</p> <p>Both fungus isolates are effective and persistent at low concentrations and short exposure times.</p

ΛΛˉ\Lambda\bar{\Lambda} Production in Two-Photon Interactions at CLEO

Using the CLEO detector at the Cornell $e^+e^-$ storage ring, CESR, we study the two-photon production of $\Lambda \bar{\Lambda}$, making the first observation of $\gamma \gamma \to \Lambda \bar{\Lambda}$. We present the cross-section for $\gamma \gamma \to \Lambda \bar{\Lambda}$ as a function of the $\gamma \gamma$ center of mass energy and compare it to that predicted by the quark-diquark model.Comment: 10 pages, postscript file also available through http://w4.lns.cornell.edu/public/CLN

Cold Induces Micro- and Nano-Scale Reorganization of Lipid Raft Markers at Mounds of T-Cell Membrane Fluctuations

Whether and how cold causes changes in cell-membrane or lipid rafts remain poorly characterized. Using the NSOM/QD and confocal imaging systems, we found that cold caused microscale redistribution of lipid raft markers, GM1 for lipid and CD59 for protein, from the peripheral part of microdomains to the central part on Jurkat T cells, and that cold also induced the nanoscale size-enlargement (1/3- to 2/3-fold) of the nanoclusters of lipid raft markers and even the colocalization of GM1 and CD59 nanoclusters. These findings indicate cold-induced lateral rearrangement/coalescence of raft-related membrane heterogeneity. The cold-induced re-distribution of lipid raft markers under a nearly-natural condition provide clues for their alternations, and help to propose a model in which raft lipids associate themselves or interact with protein components to generate functional membrane heterogeneity in response to stimulus. The data also underscore the possible cold-induced artifacts in early-described cold-related experiments and the detergent-resistance-based analyses of lipid rafts at 4°C, and provide a biophysical explanation for recently-reported cold-induced activation of signaling pathways in T cells. Importantly, our fluorescence-topographic NSOM imaging demonstrated that GM1/CD59 raft markers distributed and re-distributed at mounds but not depressions of T-cell membrane fluctuations. Such mound-top distribution of lipid raft markers or lipid rafts provides spatial advantage for lipid rafts or contact molecules interacting readily with neighboring cells or free molecules

Combining Fungal Biopesticides and Insecticide-Treated Bednets to Enhance Malaria Control

In developing strategies to control malaria vectors, there is increased interest in biological methods that do not cause instant vector mortality, but have sublethal and lethal effects at different ages and stages in the mosquito life cycle. These techniques, particularly if integrated with other vector control interventions, may produce substantial reductions in malaria transmission due to the total effect of alterations to multiple life history parameters at relevant points in the life-cycle and transmission-cycle of the vector. To quantify this effect, an analytically tractable gonotrophic cycle model of mosquito-malaria interactions is developed that unites existing continuous and discrete feeding cycle approaches. As a case study, the combined use of fungal biopesticides and insecticide treated bednets (ITNs) is considered. Low values of the equilibrium EIR and human prevalence were obtained when fungal biopesticides and ITNs were combined, even for scenarios where each intervention acting alone had relatively little impact. The effect of the combined interventions on the equilibrium EIR was at least as strong as the multiplicative effect of both interventions. For scenarios representing difficult conditions for malaria control, due to high transmission intensity and widespread insecticide resistance, the effect of the combined interventions on the equilibrium EIR was greater than the multiplicative effect, as a result of synergistic interactions between the interventions. Fungal biopesticide application was found to be most effective when ITN coverage was high, producing significant reductions in equilibrium prevalence for low levels of biopesticide coverage. By incorporating biological mechanisms relevant to vectorial capacity, continuous-time vector population models can increase their applicability to integrated vector management