Epidemiological, clinical and laboratory characteristics of 19 serologically confirmed rickettsial disease in Singapore.

AIM: To identify epidemiological, clinical and laboratory features of serologically-proven typhus in the local setting. METHOD & RESULTS: Retrospective study looking at rickettsial serologies done over a six-month period and collection of the epidemological, clinical, laboratory and treatment response data from the case notes of the patients with an ordered rickettsial serology. Twenty of the 35 cases had a positive serology. Of these 20 patients, 18 were already clinically diagnosed as having murine typhus. All except one were males and all were migrant workers. Majority of the patients were construction workers staying in containers where rats abound. The most consistent clinical features were high fever (100%) for a median period of seven days, headache (94%) and cough (47%). The white cell count was usually normal (74%) but thrombocytopenia was common (68%). Transaminitis was also common (90%) with the AST component higher than the ALT in half of the cases. Response to doxycycline therapy was rapid and most (88%) were afebrile by 72 hours. CONCLUSION: Typhus (notably murine type) can be confidently diagnosed from consistent clinical features supported by epidemiological and laboratory clues. Early recognition with the prompt treatment response will result in shorter hospital stay with decreased cost. Serological testing may only prove useful in difficult situations when the clinical diagnosis is less clear

Describing complex design practices with a cross-domain framework: learning from Synthetic Biology and Swarm Robotics

This paper reports on the development of a cross-domain framework for describing complex design practices. The framework is grounded in studies of two different complex design fields: Synthetic Biology and Swarm Robotics. In the first study, we interviewed practitioners in Synthetic Biology, identifying three essential aspects of complex design problems and practices. The first of these aspects is the characterisation of system complexity, the second is the design objective taken with respect to this complexity, and the third is the design approach applied to realise this objective. In the second study, we interviewed designers in Swarm Robotics, confirming the domain generality of the three aspects identified in the first study and permitting a comparison to be made of how the two fields differ from each other in these aspects. Considered together, the two studies provide the basis for building a cross-domain framework for describing complex design practices. Such a framework is presented here, not to exhaust all possible descriptions of complex design practice but rather to provide a structured yet adaptable way of highlighting the important aspects of these descriptions. Indeed, each aspect of complex design can be can be broken down into different elements depending on the design contexts under consideration. Having such a framework enables designers to identify fundamental similarities and differences both between and within fields.This work was funded by the UK’s Engineering and Physical Sciences Research Council (EP/K008196/1).This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s00163-016-0219-

Modeling pegylated liposomal doxorubicin-induced hand-foot syndrome and intestinal mucositis in zebrafish

[[abstract]]Pegylated liposomal doxorubicin (PLD) has been widely used to treat cancer. The adverse effects of PLD noted in clinical practice, especially hand-foot syndrome (HFS), are regarded as unique, and the management methods for them remain limited. This study was aimed at developing a feasible experimental model for translational medicine to solve this clinical issue by using skin fluorescent transgenic zebrafish. We established an optimal protocol for the administration of Lipo-Dox™, a PLD in current clinical use, to the Tg(k18:dsred) zebrafish line expressing red fluorescence in keratinocytes. We made use of bodyweight, survival rate, gross observation, flssuorescent microscopic assessment, and pathological examination of the zebrafish to assess this model. The consecutive administration protocol of PLD resulted in growth retardation of the zebrafish embryo and survival impairment, indicating establishment of a significant toxicity. We observed fin necrosis and keratinocyte dissociation phenotypes in the PLD-treated fish after consecutive administration. The skin toxicity induced by the Lipo-Dox injection was subsequently reversible, which might be compatible with a clinical course of skin recovery after discontinuation of Lipo-Dox administration. Furthermore, we found that the number of intestinal goblet cells, an important marker of intestinal inflammation, in the Lipo-Dox-injected zebrafish was markedly increased, accompanied by impaired mucosal integrity. The intestinal inflammation induced by Lipo-Dox resembled the intestinal mucositis the clinical patients suffered from after the administration of PLD. In conclusion, we established a zebrafish model for PLD-induced HFS. The intestinal mucositis simultaneously noted in the PLD-treated zebrafish validated the similarity of clinical courses after administration of PLD. This model is easily assessable, efficient, and worthy for use in developing a new therapeutic protocol for prevention or treatment of HFS as well as intestinal mucositis. Further clinical investigations to validate the correlation between human and zebrafish data are warranted.[[journaltype]]國外[[ispeerreviewed]]Y[[booktype]]電子版[[countrycodes]]GB

Controllability and controller-observer design for a class of linear time-varying systems

“The final publication is available at Springer via http://dx.doi.org/10.1007/s10852-012-9212-6"In this paper a class of linear time-varying control systems is considered. The time variation consists of a scalar time-varying coefficient multiplying the state matrix of an otherwise time-invariant system. Under very weak assumptions of this coefficient, we show that the controllability can be assessed by an algebraic rank condition, Kalman canonical decomposition is possible, and we give a method for designing a linear state-feedback controller and Luenberger observer

Analysis of chaos in current-mode-controlled dc drive systems

In this paper, chaotic behavior in current-mode-controlled dc drive systems has been analyzed. The key is to derive an iterative map that describes the nonlinear system dynamics. Analytical modeling of fundamental and subharmonic oscillations as well as their stability analysis are presented. The results show that the current-mode-controlled dc drive systems generally exhibit chaotic behavior. To avoid the occurrence of chaos, the stable ranges of various system parameters are determined. Both computer simulation and experimental measurement are given to verify the theoretical analysis.published_or_final_versio

Dynamic bifurcation in dc drives

Dynamic bifurcation as well as chaotic behavior in a fixed-frequency current-mode controlled dc chopper-fed dc motor drive system is presented. The key is to derive an iterative map that describes the nonlinear dynamics of the system operating in the continuous conduction mode. It illustrates that different bifurcation diagrams can be obtained by varying different system parameters. Analytical modeling of period-1 and hence period-p orbits as well as their stability analysis using the characteristic multipliers are also presented. Hence, those stable ranges of various system parameters can be determined. Moreover, chaotic behavior is quantified by evaluating the Lyapunov exponents. The proposed approach is so general that it can readily be applied to other current-mode dc drives.published_or_final_versio

A Machine-Synesthetic Approach To DDoS Network Attack Detection

In the authors' opinion, anomaly detection systems, or ADS, seem to be the most perspective direction in the subject of attack detection, because these systems can detect, among others, the unknown (zero-day) attacks. To detect anomalies, the authors propose to use machine synesthesia. In this case, machine synesthesia is understood as an interface that allows using image classification algorithms in the problem of detecting network anomalies, making it possible to use non-specialized image detection methods that have recently been widely and actively developed. The proposed approach is that the network traffic data is "projected" into the image. It can be seen from the experimental results that the proposed method for detecting anomalies shows high results in the detection of attacks. On a large sample, the value of the complex efficiency indicator reaches 97%.Comment: 12 pages, 2 figures, 5 tables. Accepted to the Intelligent Systems Conference (IntelliSys) 201

Specifying, detecting and analysing emergent behaviours in multi-level agent-based simulations

We introduce a method for analysing emergent behaviours in multi-agent simulations using complex events. Complex events are composed of interrelated events, and they can be defined at any level of spatio-temporal abstraction (equal to or above the lowest level of abstraction given by the model). Minimal types of complex events define sets, which are equated with particular emergent behaviours and can be detected in simulation. Since complex events are derived from the agent-based model itself, they provide significant benefits when compared with traditional state-aggregation methods. First, they provide a method of specifying emergent behaviour, so that such behaviour can be monitored. Second, they provide a mechanism that retains the underlying structure of that behaviour. This latter property supports analysis of the mechanisms at lower levels that give rise to emergent behaviours, and identification of patterns between levels. In other words, multi-agent simulations become less 'opaque' [1]

Radioactive in situ hybridization for detecting diverse gene expression patterns in tissue.

Knowing the timing, level, cellular localization, and cell type that a gene is expressed in contributes to our understanding of the function of the gene. Each of these features can be accomplished with in situ hybridization to mRNAs within cells. Here we present a radioactive in situ hybridization method modified from Clayton et al. (1988)(1) that has been working successfully in our lab for many years, especially for adult vertebrate brains(2-5). The long complementary RNA (cRNA) probes to the target sequence allows for detection of low abundance transcripts(6,7). Incorporation of radioactive nucleotides into the cRNA probes allows for further detection sensitivity of low abundance transcripts and quantitative analyses, either by light sensitive x-ray film or emulsion coated over the tissue. These detection methods provide a long-term record of target gene expression. Compared with non-radioactive probe methods, such as DIG-labeling, the radioactive probe hybridization method does not require multiple amplification steps using HRP-antibodies and/or TSA kit to detect low abundance transcripts. Therefore, this method provides a linear relation between signal intensity and targeted mRNA amounts for quantitative analysis. It allows processing 100-200 slides simultaneously. It works well for different developmental stages of embryos. Most developmental studies of gene expression use whole embryos and non-radioactive approaches(8,9), in part because embryonic tissue is more fragile than adult tissue, with less cohesion between cells, making it difficult to see boundaries between cell populations with tissue sections. In contrast, our radioactive approach, due to the larger range of sensitivity, is able to obtain higher contrast in resolution of gene expression between tissue regions, making it easier to see boundaries between populations. Using this method, researchers could reveal the possible significance of a newly identified gene, and further predict the function of the gene of interest