117 research outputs found

    Automated Analysis of Concurrent and Real-Time Software

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    This paper surveys the current status of our work on automated anal-ysis of the logical and timing properties of concurrent software based on the constrained expression approach. It describes our analysis toolset, reports some extremely encouraging results of using the toolset to ana-lyze logical properties of nontrivial concurrent systems, and discusses the modifications we have made to the toolset to apply it to analyzing tim-ing properties. It then outlines ongoing and planned research directed at further improving these methods

    cAMP-Signalling Regulates Gametocyte-Infected Erythrocyte Deformability Required for Malaria Parasite Transmission.

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    Blocking Plasmodium falciparum transmission to mosquitoes has been designated a strategic objective in the global agenda of malaria elimination. Transmission is ensured by gametocyte-infected erythrocytes (GIE) that sequester in the bone marrow and at maturation are released into peripheral blood from where they are taken up during a mosquito blood meal. Release into the blood circulation is accompanied by an increase in GIE deformability that allows them to pass through the spleen. Here, we used a microsphere matrix to mimic splenic filtration and investigated the role of cAMP-signalling in regulating GIE deformability. We demonstrated that mature GIE deformability is dependent on reduced cAMP-signalling and on increased phosphodiesterase expression in stage V gametocytes, and that parasite cAMP-dependent kinase activity contributes to the stiffness of immature gametocytes. Importantly, pharmacological agents that raise cAMP levels in transmissible stage V gametocytes render them less deformable and hence less likely to circulate through the spleen. Therefore, phosphodiesterase inhibitors that raise cAMP levels in P. falciparum infected erythrocytes, such as sildenafil, represent new candidate drugs to block transmission of malaria parasites

    Treatment outcomes of adult patients with recurrent tuberculosis in relation to HIV status in Zimbabwe: a retrospective record review

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    <p>Abstract</p> <p>Background</p> <p>Zimbabwe is a Southern African country with a high HIV-TB burden and is ranked 19<sup>th </sup>among the 22 Tuberculosis high burden countries worldwide. Recurrent TB is an important problem for TB control, yet there is limited information about treatment outcomes in relation to HIV status. This study was therefore conducted in Chitungwiza, a high density dormitory town outside the capital city, to determine in adults registered with recurrent TB how treatment outcomes were affected by type of recurrence and HIV status.</p> <p>Methods</p> <p>Data were abstracted from the Chitungwiza district TB register for all 225 adult TB patients who had previously been on anti-TB treatment and who were registered as recurrent TB from January to December 2009. The Chi-square and Fischer's exact tests were used to establish associations between categorical variables. Multivariate relative risks for associations between the various TB treatment outcomes and HIV status, type of recurrent TB, sex and age were calculated using Poisson regression with robust error variance.</p> <p>Results</p> <p>Of 225 registered TB patients with recurrent TB, 159 (71%) were HIV tested, 135 (85%) were HIV-positive and 20 (15%) were known to be on antiretroviral treatment (ART). More females were HIV-tested (75/90, 83%) compared with males (84/135, 62%). There were 103 (46%) with relapse TB, 32 (14%) with treatment after default, and 90 (40%) with "retreatment other" TB. There was one failure patient. HIV-testing and HIV-positivity were similar between patients with different types of TB. Overall, treatment success was 73% with transfer-outs at 14% being the most common adverse outcome. TB treatment outcomes did not differ by HIV status. However those with relapse TB had better treatment success compared to "retreatment other" TB patients, (adjusted RR 0.81; 95% CI 0.68 - 0.97, <it>p </it>= 0.02).</p> <p>Conclusions</p> <p>No differences in treatment outcomes by HIV status were established in patients with recurrent TB. Important lessons from this study include increasing HIV testing uptake, a better understanding of what constitutes "retreatment other" TB, improved follow-up of true outcomes in patients who transfer-out and better recording practices related to HIV care and treatment especially for ART.</p

    When Does an Alien Become a Native Species? A Vulnerable Native Mammal Recognizes and Responds to Its Long-Term Alien Predator

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    The impact of alien predators on native prey populations is often attributed to prey naiveté towards a novel threat. Yet evolutionary theory predicts that alien predators cannot remain eternally novel; prey species must either become extinct or learn and adapt to the new threat. As local enemies lose their naiveté and coexistence becomes possible, an introduced species must eventually become ‘native’. But when exactly does an alien become a native species? The dingo (Canis lupus dingo) was introduced to Australia about 4000 years ago, yet its native status remains disputed. To determine whether a vulnerable native mammal (Perameles nasuta) recognizes the close relative of the dingo, the domestic dog (Canis lupus familiaris), we surveyed local residents to determine levels of bandicoot visitation to yards with and without resident dogs. Bandicoots in this area regularly emerge from bushland to forage in residential yards at night, leaving behind tell-tale deep, conical diggings in lawns and garden beds. These diggings were less likely to appear at all, and appeared less frequently and in smaller quantities in yards with dogs than in yards with either resident cats (Felis catus) or no pets. Most dogs were kept indoors at night, meaning that bandicoots were not simply chased out of the yards or killed before they could leave diggings, but rather they recognized the threat posed by dogs and avoided those yards. Native Australian mammals have had thousands of years experience with wild dingoes, which are very closely related to domestic dogs. Our study suggests that these bandicoots may no longer be naïve towards dogs. We argue that the logical criterion for determining native status of a long-term alien species must be once its native enemies are no longer naïve

    Assessing Predation Risk to Threatened Fauna from their Prevalence in Predator Scats: Dingoes and Rodents in Arid Australia

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    The prevalence of threatened species in predator scats has often been used to gauge the risks that predators pose to threatened species, with the infrequent occurrence of a given species often considered indicative of negligible predation risks. In this study, data from 4087 dingo (Canis lupus dingo and hybrids) scats were assessed alongside additional information on predator and prey distribution, dingo control effort and predation rates to evaluate whether or not the observed frequency of threatened species in dingo scats warrants more detailed investigation of dingo predation risks to them. Three small rodents (dusky hopping-mice Notomys fuscus; fawn hopping-mice Notomys cervinus; plains mice Pseudomys australis) were the only threatened species detected in <8% of dingo scats from any given site, suggesting that dingoes might not threaten them. However, consideration of dingo control effort revealed that plains mice distribution has largely retracted to the area where dingoes have been most heavily subjected to lethal control. Assessing the hypothetical predation rates of dingoes on dusky hopping-mice revealed that dingo predation alone has the potential to depopulate local hopping-mice populations within a few months. It was concluded that the occurrence of a given prey species in predator scats may be indicative of what the predator ate under the prevailing conditions, but in isolation, such data can have a poor ability to inform predation risk assessments. Some populations of threatened fauna assumed to derive a benefit from the presence of dingoes may instead be susceptible to dingo-induced declines under certain conditions

    Blood cultures for the diagnosis of multidrug-resistant and extensively drug-resistant tuberculosis among HIV-infected patients from rural South Africa: a cross-sectional study

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    <p>Abstract</p> <p>Background</p> <p>The yield of mycobacterial blood cultures for multidrug-resistant (MDR) and extensively drug-resistant tuberculosis (XDR-TB) among drug-resistant TB suspects has not been described.</p> <p>Methods</p> <p>We performed a retrospective, cross-sectional analysis to determine the yield of mycobacterial blood cultures for MDR-TB and XDR-TB among patients suspected of drug-resistant TB from rural South Africa. Secondary outcomes included risk factors of <it>Mycobacterium tuberculosis </it>bacteremia and the additive yield of mycobacterial blood cultures compared to sputum culture.</p> <p>Results</p> <p>From 9/1/2006 to 12/31/2008, 130 patients suspected of drug-resistant TB were evaluated with mycobacterial blood culture. Each patient had a single mycobacterial blood culture with 41 (32%) positive for <it>M. tuberculosis</it>, of which 20 (49%) were XDR-TB and 8 (20%) were MDR-TB. One hundred fourteen (88%) patients were known to be HIV-infected. Patients on antiretroviral therapy were significantly less likely to have a positive blood culture for <it>M. tuberculosis </it>(p = 0.002). The diagnosis of MDR or XDR-TB was made by blood culture alone in 12 patients.</p> <p>Conclusions</p> <p>Mycobacterial blood cultures provided an additive yield for diagnosis of drug-resistant TB in patients with HIV from rural South Africa. The use of mycobacterial blood cultures should be considered in all patients suspected of drug-resistant TB in similar settings.</p

    Could Direct Killing by Larger Dingoes Have Caused the Extinction of the Thylacine from Mainland Australia?

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    Invasive predators can impose strong selection pressure on species that evolved in their absence and drive species to extinction. Interactions between coexisting predators may be particularly strong, as larger predators frequently kill smaller predators and suppress their abundances. Until 3500 years ago the marsupial thylacine was Australia's largest predator. It became extinct from the mainland soon after the arrival of a morphologically convergent placental predator, the dingo, but persisted in the absence of dingoes on the island of Tasmania until the 20th century. As Tasmanian thylacines were larger than dingoes, it has been argued that dingoes were unlikely to have caused the extinction of mainland thylacines because larger predators are rarely killed by smaller predators. By comparing Holocene specimens from the same regions of mainland Australia, we show that dingoes were similarly sized to male thylacines but considerably larger than female thylacines. Female thylacines would have been vulnerable to killing by dingoes. Such killing could have depressed the reproductive output of thylacine populations. Our results support the hypothesis that direct killing by larger dingoes drove thylacines to extinction on mainland Australia. However, attributing the extinction of the thylacine to just one cause is problematic because the arrival of dingoes coincided with another the potential extinction driver, the intensification of the human economy
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