New and emerging treatments for fungal infections

Although several new antifungal drugs have been licensed in the last 5 years, some patients remain difficult to treat. The main reasons for this include intrinsic or acquired antifungal resistance, organ dysfunction preventing the use of some agents and drug interactions. In addition, some drugs pene-trate poorly into sanctuary sites including eye and urine, and others are associated with considerable adverse events. Here, we review the preclinical and clinical development progress with four new anti-fungal agents: isavuconazole, ravuconazole, albaconazole and aminocandin. Isavuconazole and ravu-conazole are extremely similar, with a broad spectrum of activity, a very long half-life and large volume of distribution and good in vivo data supporting their efficacy in invasive aspergillosis and candidosis. Both compounds are in early Phase 3 development. Albaconazole has also shown very potent activity against species of Candida, Cryptococcus and Aspergillus. It was well tolerated and effective in women with vaginal candidosis. Aminocandin is an intravenous-only echinocandin with in vivo activity against Candida spp. and Aspergillus spp. Its extended half-life probably permits dosing less fre-quently than once a day. Overall these new antifungal agents in development offer extended half-lives, possibly reduced drug interaction profiles and good tolerance. Their antifungal spectrum is narrower than posaconazole and probably similar to voriconazole (isavuconazole and ravuconazole) and caspo-fungin (aminocandin). Licensure and determination of their place in clinical practice requires random-ized clinical studies, which are or will be underway

INTERIM REPORT IMPROVED METHODS FOR INCORPORATING RISK IN DECISION MAKING

This paper reports observations and preliminary investigations in the first phase of a research program covering methodologies for making safety-related decisions. The objective has been to gain insight into NRC perceptions of the value of formal decision methods, their possible applications, and how risk is, or may be, incorporated in decision making. The perception of formal decision making techniques, held by various decision makers, and what may be done to improve them, were explored through interviews with NRC staff. An initial survey of decision making methods, an assessment of the applicability of formal methods vis-a-vis the available information, and a review of methods of incorporating risk and uncertainty have also been conducted

Detecting control flow in Smarphones: Combining static and dynamic analyses

International audienceSecurity in embedded systems such as smartphones requires protection of confidential data and applications. Many of security mechanisms use dynamic taint analysis techniques for tracking information flow in software. But these techniques cannot detect control flows that use conditionals to implicitly transfer information from objects to other objects. In particular, malicious applications can bypass Android system and get privacy sensitive information through control flows. We propose an enhancement of dynamic taint analysis that propagates taint along control dependencies by using the static analysis in embedded system such as Google Android operating system. By using this new approach, it becomes possible to protect sensitive information and detect most types of software exploits without reporting too many false positives

Comparison of two fluorescent whiteners, Calcofluor and Blankophor, for the detection of fungal elements in clinical specimens in the diagnostic laboratory

ABSTRACTFluorescent whiteners, such as Blankophor and Calcofluor white, bind to chitin and cellulose, and fluoresce when exposed to UV light. Detection of fungal elements from skin and nail samples was faster and more accurate using Blankophor compared with potassium hydroxide preparations and Calcofluor (sensitivity and specificity 100% and 86% vs. 83–90% and 84–88%, or 80% and 84%, respectively). Visibility was improved, and the procedures were simple, inexpensive and rapid, all of which are important considerations in a busy diagnostic laboratory

Paper Session I-A - Non-Ohmic Discharge Characteristics of the JSC MARS-1 Martian Regolith Simulant

Studies of the voltage (charge) decay behavior of the JSC Mars-1 Martian Regolith simulant are presented for both moist and dry conditions in a simulated Earth/Mars environment. The results indicate that moisture content is the main driving force behind the form of the decay curve as well as temperature while atmospheric content and pressure play a little role. Dry simulant conditions act as well-behaved ohmic insulators with an expected exponential decay, while moist simulant possesses non-ohmic behavior decaying as 1/time. The decay relationships are derived from the experimental measurements of the current-voltage relationships. Some possible explanations of this behavior are discussed

Comparison of six Aspergillus-specific IgG assays for the diagnosis of chronic pulmonary aspergillosis (CPA)

Summary Objectives: Chronic pulmonary aspergillosis (CPA) is estimated to affect 3 million persons worldwide. Aspergillus-specific IgG is a key component in CPA diagnosis. We aimed to establish the optimal diagnostic cut offs for CPA and the comparative performance of six assays in this context. Methods: Sera from 241 patients with CPA and 100 healthy blood donors were tested using five Aspergillus-specific IgG assays plus precipitin testing using Microgen Aspergillus antigens. Optimal CPA diagnostic cut-offs were; ImmunoCAP 20 mg/L (96% sensitivity, 98% specificity), Immulite 10 mg/L (96% sensitivity, 98% specificity), Serion 35 U/ml (90% sensitivity, 98% specificity), Dynamiker 65 AU/ml (77% sensitivity, 97% specificity) and Genesis 20 U/ ml (75% sensitivity, 99% specificity). The precipitin test was 59% sensitive and 100% specific

The estimated burden of fungal disease in South Africa

Background. With a population of 56.5 million, over 7 million persons living with HIV, one of the world’s highest rates of tuberculosis (TB) and a large proportion of the population living in poverty, South Africa (SA)’s fungal disease burden is probably substantial and broad in scope.Objectives. To estimate the burden of fungal disease in SA.Methods. Using total and at-risk populations and national, regional and occasionally global data, we estimated the incidence and prevalence of the majority of fungal diseases in SA.Results. Estimates for the annual incidence of HIV-related life-threatening fungal disease include cryptococcal meningitis (8 357 cases), Pneumocystis pneumonia (4 452 cases) and endemic mycoses (emergomycosis, histoplasmosis and blastomycosis, with 100, 60 and 10 cases per year, respectively). We estimate 3 885 cases of invasive aspergillosis annually. The annual burden of candidaemia and Candida peritonitis is estimated at 5 421 and 1 901 cases, respectively. The epidemic of pulmonary TB has probably driven up the prevalence of chronic pulmonary aspergillosis to 99 351 (175.8/100 000), perhaps the highest in the world. Fungal asthma probably affects >100 000 adults. Mucosal candidiasis is common, with an annual prevalence estimated at 828 666 and 135 289 oral and oesophageal cases, respectively, complicating HIV infection alone (estimates in other conditions not made), and over a million women are estimated to be affected by recurrent vulvovaginal candidiasis each year. Tinea capitis in children is common and conservatively estimated at >1 000 000 cases. The inoculation mycoses sporotrichosis, chromoblastomycosis and eumycetoma occur occasionally (with 40, 40 and 10 cases estimated, respectively). Overall, we estimate that over 3.2 million South Africans are afflicted by a fungal disease each year (7.1% of the population).Conclusions. Significant numbers of South Africans are estimated to be affected each year by fungal infections, driven primarily by the syndemics of HIV, TB and poverty. These estimates emphasise the need for better epidemiological data, and for improving the diagnosis and management of these diseases

Serious fungal infections in Portugal

There is a lack of knowledge on the epidemiology of fungal infections worldwide because there are no reporting obligations. The aim of this study was to estimate the burden of fungal disease in Portugal as part of a global fungal burden project. Most published epidemiology papers reporting fungal infection rates from Portugal were identified. Where no data existed, specific populations at risk and fungal infection frequencies in those populations were used in order to estimate national incidence or prevalence, depending on the condition. An estimated 1,510,391 persons develop a skin or nail fungal infection each year. The second most common fungal infection in Portugal is recurrent vulvovaginal candidiasis, with an estimated 150,700 women (15-50 years of age) suffering from it every year. In human immunodeficiency virus (HIV)-infected people, oral or oesophageal candidiasis rates were estimated to be 19.5 and 16.8/100,000, respectively. Candidaemia affects 2.19/100,000 patients, in a total of 231 cases nationally. Invasive aspergillosis is less common than in other countries as chronic obstructive pulmonary disease (COPD) is uncommon in Portugal, a total of 240 cases annually. The estimated prevalence of chronic pulmonary aspergillosis after tuberculosis (TB) is 194 cases, whereas its prevalence for all underlying pulmonary conditions was 776 patients. Asthma is common (10% in adults) and we estimate 16,614 and 12,600 people with severe asthma with fungal sensitisation and allergic bronchopulmonary aspergillosis, respectively. Sixty-five patients develop Pneumocystis pneumonia in acquired immune deficiency syndrome (AIDS) and 13 develop cryptococcosis. Overall, we estimate a total number of 1,695,514 fungal infections starting each year in Portugal.info:eu-repo/semantics/publishedVersio

RIDA: Robust Intrusion Detection in Ad Hoc Networks

We focus on detecting intrusions in wireless ad hoc networks using the misuse detection technique. We allow for detection modules that periodically fail to detect attacks and also generate false positives. Combining theories of hypothesis testing and approximation algorithms, we develop a framework to counter different threats while minimizing the resource consumption. We obtain computationally simple optimal rules for aggregating and thereby minimizing the errors in the decisions of the nodes executing the intrusion detection software (IDS) modules. But, we show that the selection of the optimal set of nodes for executing the IDS is an NP-hard problem. We present a polynomial complexity selection algorithm that attains a guaranteeable approximation bound. We also modify this algorithm to allow for seamless operation in time varying topologies, and evaluate the efficacy of the approximation algorithm and its modifications using simulation. We identify a selection algorithm that attains a good balance between performance and complexity for attaining robust intrusion detection in ad hoc networks