Pseudomonas aeruginosa fimL regulates multiple virulence functions by intersecting with Vfr-modulated pathways

Virulence of Pseudomonas aeruginosa involves the co-ordinate expression of a range of factors including type IV pili (tfp), the type III secretion system (TTSS) and quorum sensing. Tfp are required for twitching motility, efficient biofilm formation, and for adhesion and type III secretion (TTS)-mediated damage to mammalian cells. We describe a novel gene (fimL) that is required for tfp biogenesis and function, for TTS and for normal biofilm development in P. aeruginosa. The predicted product of fimL is homologous to the N-terminal domain of ChpA, except that its putative histidine and threonine phosphotransfer sites have been replaced with glutamine. fimL mutants resemble vfr mutants in many aspects including increased autolysis, reduced levels of surface-assembled tfp and diminished production of type III secreted effectors. Expression of vfr in trans can complement fimL mutants. vfr transcription and production is reduced in fimL mutants whereas cAMP levels are unaffected. Deletion and insertion mutants of fimL frequently revert to wild-type phenotypes suggesting that an extragenic suppressor mutation is able to overcome the loss of fimL. vfr transcription and production, as well as cAMP levels, are elevated in these revertants, while Pseudomonas quinolone signal (PQS) production is reduced. These results suggest that the site(s) of spontaneous mutation is in a gene(s) which lies upstream of vfr transcription, cAMP, production, and PQS synthesis. Our studies indicate that Vfr and FimL are components of intersecting pathways that control twitching motility, TTSS and autolysis in P. aeruginosa.

Type III secretion contact-dependent model for the intracellular development of Chlamydia

The medically significant genus Chlamydia is a class of obligate intracellular bacterial pathogens that replicate within vacuoles in host eukaryotic cells termed inclusions. Chlamydia's developmental cycle involves two forms; an infectious extracellular form, known as an elementary body (EB), and a non-infectious form, known as the reticulate body (RB), that replicates inside the vacuoles of the host cells. The RB surface is covered in projections that are in intimate contact with the inclusion membrane. Late in the developmental cycle, these reticulate bodies differentiate into the elementary body form. In this paper, we present a hypothesis for the modulation of these developmental events involving the contact-dependent type III secretion (TTS) system. TTS surface projections mediate intimate contact between the RB and the inclusion membrane. Below a certain number of projections, detachment of the RB provides a signal for late differentiation of RB into EB. We use data and develop a mathematical model investigating this hypothesis. If the hypothesis proves to be accurate, then we have shown that increasing the number of inclusions per host cell will increase the number of infectious progeny EB until some optimal number of inclusions. For more inclusions than this optimum, the infectious yield is reduced because of spatial restrictions. We also predict that a reduction in the number of projections on the surface of the RB (and as early as possible during development) will significantly reduce the burst size of infectious EB particles. Many of the results predicted by the model can be tested experimentally and may lead to the identification of potential targets for drug design. © Society for Mathematical Biology 2006.

A fuzzy decision tree-based duration model for Standard Yorùbá text-to-speech synthesis

In this paper, we present syllable-based duration modelling in the context of a prosody model for Standard Yorùbá (SY) text-to-speech (TTS) synthesis applications. Our prosody model is conceptualised around a modular holistic framework. This framework is implemented using the Relational Tree (R-Tree) techniques. An important feature of our R-Tree framework is its flexibility in that it facilitates the independent implementation of the different dimensions of prosody, i.e. duration, intonation, and intensity, using different techniques and their subsequent integration. We applied the Fuzzy Decision Tree (FDT) technique to model the duration dimension. In order to evaluate the effectiveness of FDT in duration modelling, we have also developed a Classification And Regression Tree (CART) based duration model using the same speech data. Each of these models was integrated into our R-Tree based prosody model. We performed both quantitative (i.e. Root Mean Square Error (RMSE) and Correlation (Corr)) and qualitative (i.e. intelligibility and naturalness) evaluations on the two duration models. The results show that CART models the training data more accurately than FDT. The FDT model, however, shows a better ability to extrapolate from the training data since it achieved a better accuracy for the test data set. Our qualitative evaluation results show that our FDT model produces synthesised speech that is perceived to be more natural than our CART model. In addition, we also observed that the expressiveness of FDT is much better than that of CART. That is because the representation in FDT is not restricted to a set of piece-wise or discrete constant approximation. We, therefore, conclude that the FDT approach is a practical approach for duration modelling in SY TTS applications. © 2006 Elsevier Ltd. All rights reserved.

A computational model of intonation for yorùbá text-to-speech synthesis:design and analysis

In this paper we present the design and analysis of an intonation model for text-to-speech (TTS) synthesis applications using a combination of Relational Tree (RT) and Fuzzy Logic (FL) technologies. The model is demonstrated using the Standard Yorùbá (SY) language. In the proposed intonation model, phonological information extracted from text is converted into an RT. RT is a sophisticated data structure that represents the peaks and valleys as well as the spatial structure of a waveform symbolically in the form of trees. An initial approximation to the RT, called Skeletal Tree (ST), is first generated algorithmically. The exact numerical values of the peaks and valleys on the ST is then computed using FL. Quantitative analysis of the result gives RMSE of 0.56 and 0.71 for peak and valley respectively. Mean Opinion Scores (MOS) of 9.5 and 6.8, on a scale of 1 - -10, was obtained for intelligibility and naturalness respectively.

Using sonic enhancement to augment non-visual tabular navigation

More information is now readily available to computer users than at any time in human history; however, much of this information is often inaccessible to people with blindness or low-vision, for whom information must be presented non-visually. Currently, screen readers are able to verbalize on-screen text using text-to-speech (TTS) synthesis; however, much of this vocalization is inadequate for browsing the Internet. An auditory interface that incorporates auditory-spatial orientation was created and tested. For information that can be structured as a two-dimensional table, links can be semantically grouped as cells in a row within an auditory table, which provides a consistent structure for auditory navigation. An auditory display prototype was tested.^ Sixteen legally blind subjects participated in this research study. Results demonstrated that stereo panning was an effective technique for audio-spatially orienting non-visual navigation in a five-row, six-column HTML table as compared to a centered, stationary synthesized voice. These results were based on measuring the time- to-target (TTT), or the amount of time elapsed from the first prompting to the selection of each tabular link. Preliminary analysis of the TTT values recorded during the experiment showed that the populations did not conform to the ANOVA requirements of normality and equality of variances. Therefore, the data were transformed using the natural logarithm. The repeated-measures two-factor ANOVA results show that the logarithmically-transformed TTTs were significantly affected by the tonal variation method, F(1,15) = 6.194, p= 0.025. Similarly, the results show that the logarithmically transformed TTTs were marginally affected by the stereo spatialization method, F(1,15) = 4.240, p=0.057. The results show that the logarithmically transformed TTTs were not significantly affected by the interaction of both methods, F(1,15) = 1.381, p=0.258. These results suggest that some confusion may be caused in the subject when employing both of these methods simultaneously. The significant effect of tonal variation indicates that the effect is actually increasing the average TTT. In other words, the presence of preceding tones increases task completion time on average. The marginally-significant effect of stereo spatialization decreases the average log(TTT) from 2.405 to 2.264.^

Evaluation of Tottenham Thinking Space Pilot: Final Report. Research Report 11.

This reports summarises research that began in March 2014 and was completed in October 2015 by an experienced inter-disciplinary research team from the Centre for Social Justice and Change and Psycho-Social Research Group, School of Social Sciences, the University of East London (UEL) and included Dr Yang Li from the Centre for Geo-Information Studies, UEL, for the first phase of the study. Tottenham ‘Thinking Space’ (TTS) was a pilot therapeutic initiative based in local communities and delivered by the Tavistock & Portman NHS Foundation Trust and funded by the London Borough of Haringey Directorate of Public Health. TTS aimed to improve mental health and enable and empower local communities. TTS was situated within a mental health agenda that was integral to Haringey’s Health and Wellbeing Strategy 2012-2015 and aimed to encourage people to help themselves and each other and develop confident communities. On the one hand TTS was well-suited to this agenda, but, on the other, participants were resistant to, and were trying to free themselves from labelling that implied ‘mental health difficulties’. A total of 243 meetings were held and 351 people attended 1,716 times. The majority of participants attended four times or less, and 33 people attended between 5 and 10 times and 39 people attended over 10 times. Attending a small number of times does not necessarily mean that the attendee was not helped. Attendees reflected the ethnic diversity of Tottenham; 29 different ethnic groups attended. The opportunity to meet with people from different cultural backgrounds in a safe space was highly valued by attendees. Similarly, participants valued the wide age range represented and felt that they benefited from listening to inter-generational experiences. The majority of participants were women (72%) and they were instrumental in initiating further Thinking Spaces, topic specific meetings, the summer programme of activities for mothers and young children and training to meet their needs. The community development worker had a key role in implementing the initiative and sustaining its growth throughout the pilot period. We observed that TTS attracted those whose life experiences were marked by personal struggle and trauma. Many participants felt safe enough to disclose mental health difficulties (85% of those who completed a questionnaire). Participants also came seeking a stronger sense of community in their local area. Key features of the meetings are that they are democratic, non-judgemental, respectful, and focussed on encouraging everyone to listen and to try to understand. We found that the therapeutic method was put in place by high quality facilitators and health and personal outcomes for participants were consistent with those predicted by the underpinning psychoanalytical and systemic theories. Outcomes included a reduction in anxieties and improved personal and social functioning; approximately two thirds of those who completed a questionnaire felt better understood, felt more motivated and more hopeful for the future. The overwhelming majority of survey respondents also felt good about contributing to their community, said that they were more able to cooperate with others and accepting of other cultures, and had made new friends. Participants typically had a better understanding of their current situation and how to take positive action; of those who completed a questionnaire, over half felt more confident to seek support for a personal issue and to contact services. Members of TTS supported each other and instilled hope and build community-mindedness that reduced social isolation.

Utilización de la fase armónica en la detección de voz sintética.

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Self-medication on the students of the school of health from Polytechnic Institute of Bragança

The self-medicatíon is a phenomenon more and more frequent and used for several years already, and tts incidence and dlstribution are related wtth the organizatíon and health system of each country. Following Medeiros thoughts (2011), this practíce conststs in the consumptíon of a medicine with the purpose of treating or relieving the symptoms and diseases or even promote self health, without using a professional prescription. Methods: With thts study, we intend to find the self-medication practice incidence on the students in the School of Health of Polytechnic Institute of Bragança (ESSa), identify the motives that lead these students to resort to this methods and identify the most used medicatíons. lt's a transversal descriptive, observational and quantítative study. To obtain the best results it was applied a questíonnaire built for that purpose. The statístícs analyses was made using Excel program. Our sample hás 219 students of the School of Health from Polytechntc Instítute of Bragança. Results: The studied sample includes 194 female and 25 male students distributed as follows: 36 frequenting Biomedical Laboratory Sdences, 26 Dietetics and Nutrition, 99 Nursing, 33 Gerontology and 22 studying Pharmacy. The self-medicatíon prevalence was 98%. The most used medicines was the analgesics and antipyretics with 86%. The most prevalent reason for the use of self-medicatíon was the thought that the disease was a "minor health issue". It was also considered a risky practice by 77% of the students. Conclusions: The self-medication is an evident practíce on the ESSa students. This results reveal some contradiction stnce the most consider 1t as a risky practíce, however it is, stíll, practíced.

Timeliness, efficiency and public procurement in hip surgery in Italy

Considering different perspectives, the scope of this thesis is to investigate how to improve healthcare resources allocation and the provision efficiency for hip surgeries, a resource-intensive operation, among the most frequently performed on the elderly, with a trend in volume that is increasing in years due to population aging. Firstly, the effect of Time-To-Surgery (TTS) on mortality for hip fracture patients is investigated. The analysis attempts to account for TTS endogeneity due to the inability to fully control for variables affecting patient delay – e.g. patient severity. Exploiting an instrumental variable model, where being admitted on Friday or Saturday predicts longer TTS, findings show exogenous TTS does not have a significant effect on mortality. Thus suggesting surgeons prioritize patients effectively, neutralizing the adverse impact of longer TTS. Then, the volume-outcome relation for total hip replacement surgery is analyzed, seeking to account for selective referral, which may be present in elective surgery context, and induce reverse causality issue in the volume-outcome relation. The analysis employs a conditional choice model where patient travel distance from all regions' hospitals is used as a hospital choice predictor. Findings show the exogenous hospital volume significantly decreases adverse outcomes probability, especially in the short run. Finally, the change in public procurement design enforced in the Romagna LHA (Italy) is exploited to assess its impact on hip prostheses cost, surgeons' implant choice, and patient health outcomes. Hip prostheses are the major cost-driver of hip replacement surgeries, hence it is crucial to design the public tender such that implant prices are minimized, but cost-containment policies have to be weighted with patient well-being. Evidence shows that a cost reduction occurred without a significant surgeons’ choices impact. Positive or no effect of surgeons specialization is found on patients outcomes after the new procurement introduction.