Mathematical modelling of schistosomiasis japonica: comparison of control strategies in the People's Republic of China

We present the first mathematical model on the transmission dynamics of Schistosoma japonicum. The work extends Barbour's classic model of schistosome transmission. It allows for the mammalian host heterogeneity characteristic of the S. japonicum life cycle, and solves the problem of under-specification of Barbour's model by the use of Chinese data we are collecting on human-bovine transmission in the Poyang Lake area of Jiangxi Province in China. The model predicts that in the lake/marshland areas of the Yangtze River basin: (1) once-early mass chemotherapy of humans is little better than twice-yearly mass chemotherapy in reducing human prevalence. Depending on the heterogeneity of prevalence within the population, targeted treatment of high prevalence groups, with lower overall coverage, can be more effective than mass treatment with higher overall coverage. Treatment confers a short term benefit only, with prevalence rising to endemic levels once chemotherapy programs are stopped (2) depending on the relative contributions of bovines and humans, bovine treatment can benefit humans almost as much as human treatment. Like human treatment, bovine treatment confers a short-term benefit. A combination of human and bovine treatment will dramatically reduce human prevalence and maintains the reduction for a longer period of time than treatment of a single host, although human prevalence rises once treatment ceases; (3) assuming 75% coverage of bovines, a bovine vaccine which acts on worm fecundity must have about 75% efficacy to reduce the reproduction rate below one and ensure mid-term reduction and long-term elimination of the parasite. Such a vaccination program should be accompanied by an initial period of human treatment to instigate a short-term reduction in prevalence, following which the reduction is enhanced by vaccine effects; (4) if the bovine vaccine is only 45% efficacious (the level of current prototype vaccines) it will lower the endemic prevalence, but will not result in elimination. If it is accompanied by an initial period of human treatment and by a 45% improvement in human sanitation or a 30% reduction in contaminated water contact by humans, elimination is then possible. (C) 2002 Elsevier Science B.V. All rights reserved.

NPS-2143 - Treatment of osteoporosis - Calcilytic

Efforts to discover new treatments for osteoporosis led to the identification of the potent and selective, small-molecule calcium receptor antagonist NPS-2143. NPS-2143 is the prototype calcilytic drug, designed to act on calcium receptors on the surface of parathyroid glands, stimulating the release of the body's own stores of native parathyroid hormone (PTH). In osteopenic ovariectomized rats, daily oral administration of NPS-2143 resulted in moderate but sustained increases in plasma PTH levels and marked increases in bone formation and resorption, with no net bone gain or loss. The combination of NPS-2143 and estrogen increases bone formation and density to a greater extent than either agent alone. These results suggest that NPS-2143 may be useful in the treatment of established osteoporosis.

eMelanoBase: An online locus-specific variant database for familial melanoma

A proportion of melanoma,prone individuals in both familial and non,familial contexts has been shown to carry inactivating mutations in either CDKN2A or, rarely, CDK4. CDKN2A is a complex locus that encodes two unrelated proteins from alternately spliced transcripts that are read in different frames. The alpha transcript (exons 1a, 2, and 3) produces the p16INK4A cyclin-dependent kinase inhibitor, while the beta transcript (exons 1beta and 2) is translated as p14ARF, a stabilizing factor of p53 levels through binding to MDM2. Mutations in exon 2 can impair both polypeptides and insertions and deletions in exons 1alpha, 1beta, and 2, which can theoretically generate p16INK4A,p14ARF fusion proteins. No online database currently takes into account all the consequences of these genotypes, a situation compounded by some problematic previous annotations of CDKN2A related sequences and descriptions of their mutations. As an initiative of the international Melanoma Genetics Consortium, we have therefore established a database of germline variants observed in all loci implicated in familial melanoma susceptibility. Such a comprehensive, publicly accessible database is an essential foundation for research on melanoma susceptibility and its clinical application. Our database serves two types of data as defined by HUGO. The core dataset includes the nucleotide variants on the genomic and transcript levels, amino acid variants, and citation. The ancillary dataset includes keyword description of events at the transcription and translation levels and epidemiological data. The application that handles users' queries was designed in the model,view. controller architecture and was implemented in Java. The object-relational database schema was deduced using functional dependency analysis. We hereby present our first functional prototype of eMelanoBase. The service is accessible via the URL www.wmi.usyd.e, du.au:8080/melanoma.html.

Polymerase chain reaction tests for the identification of Ross River, Kunjin and Murray Valley encephalitis virus infections in horses

Objective To develop and validate specific, sensitive and rapid diagnostic tests using RT-PCR for the detection of Ross River virus (RRV), Kunjin virus (KV) and Murray Valley encephalitis virus (MVEV) infections in horses. Methods Primer sets based on nucleotide sequence encoding the envelope glycoprotein E2 of RRV and on the nonstructural protein 5 (NS5) of KV and MVEV were designed and used in single round PCRs to test for the respective viruses in infected cell cultures and, in the case of RRV, in samples of horse blood and synovial fluid. Results The primer pairs designed for each of the three viruses amplified a product of expected size from prototype viruses that were grown in cell culture. The identity of each of the products was confirmed by nucleotide sequencing indicating that in the context used the RT-PCRs were specific. RRV was detected in serums from 8 horses for which there were clinical signs consistent with RRV infection such that an acute-phase serum sample was taken and submitted for RRV serology testing. The RRV RT-PCR was analytically sensitive in that it was estimated to detect as little as 50 TCID50 of RRV per mL of serum and was specific in that the primer pairs did not amplify other products from the 8 serum samples. The RRV primers also detected virus in three independent mosquito pools known to contain RRV by virus isolation in cell culture. Samples from horses suspected to be infected with KV and MVEV were not available. Conclusion Despite much anecdotal and serological evidence for infection of horses with RRV actual infection and associated clinical disease are infrequently confirmed. The availability of a specific and analytically sensitive RT-PCR for the detection of RRV provides additional opportunities to confirm the presence of this virus in clinical samples. The RTPCR primers for the diagnosis of KV and MVEV infections were shown to be specific for cell culture grown viruses but the further validation of these tests requires the availability of appropriate clinical samples from infected horses.

Complete genomic sequence of the Australian south-west genotype of Sindbis virus: Comparisons with other Sindbis strains and identification of a unique deletion in the 3 '-untranslated region

Our previous studies have shown that two distinct genotypes of Sindbis (SIN) virus occur in Australia. One of these, the Oriental/Australian type, circulates throughout most of the Australian continent, whereas the recently identified south-west (SW) genetic type appears to be restricted to a distinct geographic region located in the temperate south-west of Australia. We have now determined the complete nucleotide and translated amino acid sequences of a SW isolate of SIN virus (SW6562) and performed comparative analyses with other SIN viruses at the genomic level. The genome of SW6562 is 11,569 nucleotides in length, excluding the cap nucleotide and poly (A) tail. Overall this virus differs from the prototype SIN virus (strain AR339) by 23% in nucleotide sequence and 12.5% in amino acid sequence. Partial sequences of four regions of the genome of four SW isolates were determined and compared with the corresponding sequences from a number of SIN isolates from different regions of the World. These regions are the non-structural protein (nsP3), the E2 gene, the capsid gene, and the repeated sequence elements (RSE) of the 3'UTR. These comparisons revealed that the SW SIN viruses were more closely related to South African and European strains than to other Australian isolates of SIN virus. Thus the SW genotype of SIN virus may have been introduced into this region of Australia by viremic humans or migratory birds and subsequently evolved independently in the region. The sequence data also revealed that the SW genotype contains a unique deletion in the RSE of the 3'UTR region of the genome. Previous studies have shown that deletions in this region of the SIN genome can have significant effects on virus replication in mosquito and avian cells, which may explain the restricted distribution of this genotype of SIN virus.

Knowledge-based system on optimum design of liquid retaining structures with genetic algorithms

This paper delineates the development of a prototype hybrid knowledge-based system for the optimum design of liquid retaining structures by coupling the blackboard architecture, an expert system shell VISUAL RULE STUDIO and genetic algorithm (GA). Through custom-built interactive graphical user interfaces under a user-friendly environment, the user is directed throughout the design process, which includes preliminary design, load specification, model generation, finite element analysis, code compliance checking, and member sizing optimization. For structural optimization, GA is applied to the minimum cost design of structural systems with discrete reinforced concrete sections. The design of a typical example of the liquid retaining structure is illustrated. The results demonstrate extraordinarily converging speed as near-optimal solutions are acquired after merely exploration of a small portion of the search space. This system can act as a consultant to assist novice designers in the design of liquid retaining structures.

A coupled knowledge-based expert system for design of liquid-retaining structures

This paper describes a coupled knowledge-based system (KBS) for the design of liquid-retaining structures, which can handle both the symbolic knowledge processing based on engineering heuristics in the preliminary synthesis stage and the extensive numerical crunching involved in the detailed analysis stage. The prototype system is developed by employing blackboard architecture and a commercial shell VISUAL RULE STUDIO. Its present scope covers design of three types of liquid-retaining structures, namely, a rectangular shape with one compartment, a rectangular shape with two compartments and a circular shape. Through custom-built interactive graphical user interfaces, the user is directed throughout the design process, which includes preliminary design, load specification, model generation, finite element analysis, code compliance checking and member sizing optimization. It is also integrated with various relational databases that provide the system with sectional properties, moment and shear coefficients and final member details. This system can act as a consultant to assist novice designers in the design of liquid-retaining structures with increase in efficiency and optimization of design output and automated record keeping. The design of a typical example of the liquid-retaining structure is also illustrated. (C) 2003 Elsevier B.V All rights reserved.

The decentralized social networking systems towards mobilizing actions of citizenship and solidarity against cancer

The goal of the present study is mapping the nature of possible contributions of participatory online platforms in citizen actions that may contribute in the fight against cancer and its associated consequences. These platforms are usually associated with entertainment: in that sense, we intent to test their validity in other domains such as health, as well as contribute to an expanded perception of their potential by their users. The research is based on the analysis of online solidarity networks, namely the ones residing on Facebook, Orkut and the blogosphere, that citizens have been gradually resorting to. The research is also based on the development of newer and more efficient solutions that provide the individual (directly or indirectly affected by issues of oncology) with the means to overcome feelings of impotence and fatality. In this article, we aim at summarizing the processes of usage of these decentralized, freer participatory platforms by citizens and institutions, while attempting to unravel existing hype and stigma; we also provide a first survey of the importance and the role of institutions in this kind of endeavor; lastly, we present a prototype, developed in the context of the present study, that is specifically dedicated to addressing oncology through social media. This prototype is already available online at www.talkingaboutcancer.org, however, still under development and testing. The main objective of this platform is to allow every citizen to freely build their network of contacts and information, according to their own individual and/ or collective needs and desires.

Towards the design of efficient nonbeacon-enabled ZigBee networks

This paper presents experimental results of the communication performance evaluation of a prototype ZigBee-based patient monitoring system commissioned in an in-patient floor of a Portuguese hospital (HPG – Hospital Privado de Guimar~aes). Besides, it revisits relevant problems that affect the performance of nonbeacon-enabled ZigBee networks. Initially, the presence of hidden-nodes and the impact of sensor node mobility are discussed. It was observed, for instance, that the message delivery ratio in a star network consisting of six wireless electrocardiogram sensor devices may decrease from 100% when no hidden-nodes are present to 83.96% when half of the sensor devices are unable to detect the transmissions made by the other half. An additional aspect which affects the communication reliability is a deadlock condition that can occur if routers are unable to process incoming packets during the backoff part of the CSMA-CA mechanism. A simple approach to increase the message delivery ratio in this case is proposed and its effectiveness is verified. The discussion and results presented in this paper aim to contribute to the design of efficient networks,and are valid to other scenarios and environments rather than hospitals.

Participatory Online Platforms and the Construction of Citizen’s Autonomy in Health Issues

The goal of the present study is mapping the nature of possible contributions of participatory online platforms in citizen actions that may contribute in the fight against cancer and its associated consequences. The research is based on the analysis of online solidarity networks, namely the ones residing on Facebook and the blogosphere, that citizens have been gradually resorting to. The research is also based on the development of newer and more efficient solutions that provide the individual (directly or indirectly affected by issues of oncology) with the means to overcome feelings of impotence and fatality. In this chapter, the authors summarize the processes of usage of these decentralized, freer participatory platforms by citizens and institutions, while attempting to unravel existing hype and stigma; the authors also provide a first survey of the importance and the role of institutions in this kind of endeavor; lastly, they present a prototype, developed in the context of the present study that is specifically dedicated to addressing oncology through social media.

A laparoscopic surgery training interface

Laparoscopy is a surgical procedure on which operations in the abdomen are performed through small incisions using several specialized instruments. The laparoscopic surgery success greatly depends on surgeon skills and training. To achieve these technical high-standards, different apprenticeship methods have been developed, many based on in vivo training, an approach that involves high costs and complex setup procedures. This paper explores Virtual Reality (VR) simulation as an alternative for novice surgeons training. Even though several simulators are available on the market claiming successful training experiences, their use is extremely limited due to the economic costs involved. In this work, we present a low-cost laparoscopy simulator able to monitor and assist the trainee’s surgical movements. The developed prototype consists of a set of inexpensive sensors, namely an accelerometer, a gyroscope, a magnetometer and a flex sensor, attached to specific laparoscopic instruments. Our approach allows repeated assisted training of an exercise, without time constraints or additional costs, since no human artificial model is needed. A case study of our simulator applied to instrument manipulation practice (hand-eye coordination) is also presented.

A Generic Library for GUI Reasoning and Testing

Graphical user interfaces (GUIs) make software easy to use by providing the user with visual controls. Therefore, correctness of GUI's code is essential to the correct execution of the overall software. Models can help in the evaluation of interactive applications by allowing designers to concentrate on its more important aspects. This paper presents a generic model for language-independent reverse engineering of graphical user interface based applications, and we explore the integration of model-based testing techniques in our approach, thus allowing us to perform fault detection. A prototype tool has been constructed, which is already capable of deriving and testing a user interface behavioral model of applications written in Java/Swing.

Higher-order lazy functional slicing

Program slicing is a well known family of techniques intended to identify and isolate code fragments which depend on, or are depended upon, specific program entities. This is particularly useful in the areas of reverse engineering, program understanding, testing and software maintenance. Most slicing methods, and corresponding tools, target either the imperative or the object oriented paradigms, where program slices are computed with respect to a variable or a program statement. Taking a complementary point of view, this paper focuses on the slicing of higher-order functional programs under a lazy evaluation strategy. A prototype of a Haskell slicer, built as proof-of-concept for these ideas, is also introduced

SHACC: a functional prototyper for a component calculus

Over the last decade component-based software development arose as a promising paradigm to deal with the ever increasing complexity in software design, evolution and reuse. SHACC is a prototyping tool for component-based systems in which components are modelled coinductively as generalized Mealy machines. The prototype is built as a HASKELL library endowed with a graphical user interface developed in Swing

On the specification of a component repository

The lack of a commonly accepted de nition of a software component, the proliferation of competing `standards' and component frameworks, is here to stay, raising the fundamental question in component-based development of how to cope in practice with heterogeneity. This paper reports on the design of a Component Repository aimed to give at least a partial answer to the above question. The repository was fully speci ed in Vdm and a working prototype is currently being used in an industrial environment