Relative Contribution of P5 and Hap Surface Proteins to Nontypable Haemophilus influenzae Interplay with the Host Upper and Lower Airways

Nontypable Haemophilus influenzae (NTHi) is a major cause of opportunistic respiratory tract disease, and initiates infection by colonizing the nasopharynx. Bacterial surface proteins play determining roles in the NTHi-airways interplay, but their specific and relative contribution to colonization and infection of the respiratory tract has not been addressed comprehensively. In this study, we focused on the ompP5 and hap genes, present in all H. influenzae genome sequenced isolates, and encoding the P5 and Hap surface proteins, respectively. We employed isogenic single and double mutants of the ompP5 and hap genes generated in the pathogenic strain NTHi375 to evaluate P5 and Hap contribution to biofilm growth under continuous flow, to NTHi adhesion, and invasion/phagocytosis on nasal, pharyngeal, bronchial, alveolar cultured epithelial cells and alveolar macrophages, and to NTHi murine pulmonary infection. We show that P5 is not required for bacterial biofilm growth, but it is involved in NTHi interplay with respiratory cells and in mouse lung infection. Mechanistically, P5NTHi375 is not a ligand for CEACAM1 or α5 integrin receptors. Hap involvement in NTHi375-host interaction was shown to be limited, despite promoting bacterial cell adhesion when expressed in H. influenzae RdKW20. We also show that Hap does not contribute to bacterial biofilm growth, and that its absence partially restores the deficiency in lung infection observed for the ΔompP5 mutant. Altogether, this work frames the relative importance of the P5 and Hap surface proteins in NTHi virulence.

Advanced design optimization of cold-formed steel portal frame buildings

The design optimization of cold-formed steel portal frame buildings is considered in this paper. The objective function is based on the cost of the members for the main frame and secondary members (i.e., purlins, girts, and cladding for walls and roofs) per unit area on the plan of the building. A real-coded niching genetic algorithm is used to minimize the cost of the frame and secondary members that are designed on the basis of ultimate limit state. It iis shown that the proposed algorithm shows effective and robust capacity in generating the optimal solution, owing to the population's diversity being maintained by applying the niching method. In the optimal design, the cost of purlins and side rails are shown to account for 25% of the total cost; the main frame members account for 27% of the total cost, claddings for the walls and roofs accounted for 27% of the total cost.

The Robustness of Periodic Orchestrations in Uncertain Evolving Environments

A framework for assessing the robustness of long-duration repetitive orchestrations in uncertain evolving environments is proposed. The model assumes that service-based evaluation environments are stable over short time-frames only; over longer periods service-based environments evolve as demand fluctuates and contention for shared resources varies. The behaviour of a short-duration orchestration E in a stable environment is assessed by an uncertainty profile U and a corresponding zero-sum angel-daemon game Γ(U) [2]. Here the angel-daemon approach is extended to assess evolving environments by means of a subfamily of stochastic games. These games are called strategy oblivious because their transition probabilities are strategy independent. It is shown that the value of a strategy oblivious stochastic game is well defined and that it can be computed by solving a linear system. Finally, the proposed stochastic framework is used to assess the evolution of the Gabrmn IT system.

Establishing a population-based patient-reported outcomes study (PROMs) using national cancer registries across two jurisdictions: The Prostate Cancer Treatment, your experience (PiCTure) study

Objective: To establish an international patient-reported outcomes (PROMs) study among prostate cancer survivors, up to 18 years postdiagnosis, in two countries with different healthcare systems and ethical frameworks. Design: A cross-sectional, postal survey of prostate cancer survivors sampled and recruited via two population-based cancer registries. Healthcare professionals (HCPs) evaluated patients for eligibility to participate. Questionnaires contained validated instruments to assess health-related quality of life and psychological well-being, including QLQ-C30, QLQPR-25, EQ-5D-5L, 21-question Depression, Anxiety and Stress Scale (DASS-21) and the Decisional Regret Scale. Setting: Republic of Ireland (RoI) and Northern Ireland (NI). Primary outcome measures: Registration completeness, predictors of eligibility and response, data missingness, unweighted and weighted PROMs. Results: Prostate cancer registration was 80% (95% CI 75% to 84%) and 91% (95% CI 89% to 93%) complete 2 years postdiagnosis in NI and RoI, respectively. Of 12 322 survivors sampled from registries, 53% (n=6559) were classified as eligible following HCP screening. In the multivariate analysis, significant predictors of eligibility were: being ≤59 years of age at diagnosis (p<0.001), short-term survivor (<5 years postdiagnosis; p<0.001) and from RoI (p<0.001). 3348 completed the questionnaire, yielding a 54% adjusted response rate. 13% of men or their families called the study freephone with queries for assistance with questionnaire completion or to talk about their experience. Significant predictors of response in multivariate analysis were: being ≤59 years at diagnosis (p<0.001) and from RoI (p=0.016). Mean number of missing questions in validated instruments ranged from 0.12 (SD 0.71; EQ-5D-5L) to 3.72 (SD 6.30; QLQ-PR25). Weighted and unweighted mean EQ-5D-5L, QLQ-C30 and QLQ-PR25 scores were similar, as were the weighted and unweighted prevalences of depression, anxiety and distress. Conclusions: It was feasible to perform PROMs studies across jurisdictions, using cancer registries as sampling frames; we amassed one of the largest, international, population-based data set of prostate cancer survivors. We highlight improvements which could inform future PROMs studies, including utilising general practitioners to assess eligibility and providing a freephone service.

Gender, religion, and sociopolitical issues in cross-cultural online education

Cross-cultural education is thought to develop critical consciousness of how unequal distributions of power and privilege affect people’s health. Learners in different sociopolitical settings can join together in developing critical consciousness – awareness of power and privilege dynamics in society – by means of communication technology. The aim of this research was to define strengths and limitations of existing cross-cultural discussions in generating critical consciousness. The setting was the FAIMER international fellowship program for mid-career interdisciplinary health faculty, whose goal is to foster global advancement of health professions education. Fellows take part in participant-led, online, written, task-focused discussions on topics like professionalism, community health, and leadership. We reflexively identified text that brought sociopolitical topics into the online environment during the years 2011 and 2012 and used a discourse analysis toolset to make our content analysis relevant to critical consciousness. While references to participants’ cultures and backgrounds were infrequent, narratives of political-, gender-, religion-, and other culture-related topics did emerge. When participants gave accounts of their experiences and exchanged cross-cultural stories, they were more likely to develop ad hoc networks to support one another in facing those issues than explore issues relating to the development of critical consciousness. We suggest that cross-cultural discussions need to be facilitated actively to transform learners’ frames of reference, create critical consciousness, and develop cultural competence. Further research is needed into how to provide a safe environment for such learning and provide faculty development for the skills needed to facilitate these exchanges.

A bond model for DEM simulation of cementitious materials and deformable structures

There is an increasing use of the discrete element method (DEM) to study cemented (e.g. concrete and rocks) and sintered particulate materials. The chief advantage of the DEM over continuum based techniques is that it does not make assumptions about how cracking and fragmentation initiate and propagate, since the DEM system is naturally discontinuous. The ability for the DEM to produce a realistic representation of a cemented granular material depends largely on the implementation of an inter-particle bonded contact model. This paper presents a new bonded contact model based on the Timoshenko beam theory which considers axial, shear and bending behaviour of the bond. The bond model was first verified by simulating both the bending and dynamic response of a simply supported beam. The loading response of a concrete cylinder was then investigated and compared with the Eurocode equation prediction. The results show significant potential for the new model to produce satisfactory predictions for cementitious materials. A unique feature of this model is that it can also be used to accurately represent many deformable structures such as frames and shells, so that both particles and structures or deformable boundaries can be described in the same DEM framework. 

Amphiphysin is a component of clathrin coats formed during synaptic vesicle recycling at the lamprey giant synapse

Amphiphysin is a protein enriched at mammalian synapses thought to function as a clathrin accessory factor in synaptic vesicle endocytosis. Here we examine the involvement of amphiphysin in synaptic vesicle recycling at the giant synapse in the lamprey. We show that amphiphysin resides in the synaptic vesicle cluster at rest and relocates to sites of endocytosis during synaptic activity. It accumulates at coated pits where its SH3 domain, but not its central clathrin/AP-2-binding (CLAP) region, is accessible for antibody binding. Microinjection of antibodies specifically directed against the CLAP region inhibited recycling of synaptic vesicles and caused accumulation of clathrin-coated intermediates with distorted morphology, including flat patches of coated presynaptic membrane. Our data provide evidence for an activity-dependent redistribution of amphiphysin in intact nerve terminals and show that amphiphysin is a component of presynaptic clathrin-coated intermediates formed during synaptic vesicle recycling.

Spectacle design preferences among Chinese primary and secondary students and their parents: A qualitative and quantitative study

Purpose: To identify the specific characteristics making glasses designs, particularly those compatible with adjustable glasses, more or less appealing to Chinese children and their parents. Patients and Methods: Primary and secondary school children from urban and rural China with < = -1.00 diopters of bilateral myopia and their parents ranked four conventional-style frames identified by local optical shops as popular versus four child-specific frames compatible with adjustable spectacles. Scores based on the proportion of maximum possible ranking were computed for each style. Selected children and their parents also participated in Focus Groups (FGs) discussing spectacle design preference. Recordings were transcribed and coded by two independents reviewers using NVivo software. Results: Among 136 urban primary school children (age range 9-11 years), 290 rural secondary school children (11-17 years) and 16 parents, all adjustable-style frames (scores on 0-100 scale 25.7-62.4) were ranked behind all conventional frames (63.0-87.5). For eight FGs including 12 primary children, 26 secondary children and 16 parents, average kappa values for NVivo coding were 0.81 (students) and 0.70 (parents). All groups agreed that the key changes to make adjustable designs more attractive were altering the round lenses to rectangular or oval shapes and adding curved earpieces for more stable wear. The thick frames of the adjustable designs were considered stylish, and children indicated they would wear them if the lens shape were modified. Conclusions: Current adjustable lens designs are unattractive to Chinese children and their parents, though this study identified specific modifications which would make them more appealing.

Handbook of International Special Education:Northern Ireland

The intent of the Handbook of International Special Education is to provide a concise overview of special education services in countries across the world using the Article on Education in the United Nations Convention on the Rights of Persons with Disabilities as the analytical frame. The Handbook will provide concise, data-driven contributions from across the globe using two primary frames: the relationship between special and general education in the country and the country’s system as aligned with the Article on Education in the UN Convention on the Rights of Person with Disabilities.

Infra-estrutura para portal internet integrador de serviços

Esta tese surge no contexto de sistemas e serviços web. O objectivo é propor uma solução para o problema da integração de informação de diversas fontes, numa plataforma web única, personalizável e adaptável ao utilizador. Nos casos de empresas ou organizações que tenham para diferentes tarefas, diferentes sistemas de informação independentes, o problema da integração de informação surge com a necessidade de integração destes numa única interface disponibilizada aos seus utilizadores. A integração de serviços numa mesma interface pressupõe que haja comunicação entre um sistema central (que fornece a interface) e os diversos sistemas existentes (que detêm a totalidade – ou parte – da informação a apresentar). Assim, será necessário garantir a identidade do utilizador a cada um dos serviços apresentados, bem como assegurar que cada utilizador tem à sua disposição de forma centralizada, apenas e só a informação e operações a que realmente tem acesso em cada um dos sistemas. Trata-se de uma plataforma que pretende por um lado, fornecer a informação correcta e orientada ao utilizador e, por outro lado, garantir que a organização que suporta o sistema consegue informar e interagir com os seus utilizadores de forma mais eficaz. O cenário adoptado é a Universidade de Aveiro. Esta pretende disponibilizar uma plataforma electrónica, onde os diferentes interlocutores (alunos, docentes, funcionários, ex-alunos, etc.) possam ter acesso a informação dirigida e orientada aos seus interesses e funções na Universidade. De modo a que cada utilizador seja realmente visto como um utilizador único, serão estudados e comparados serviços de modelação de utilizador e perfis de utilizador. Será proposto um serviço de modelação de utilizador e uma lógica de criação de perfis de utilizador, distintos do existente no estado de arte. Esta lógica conjuga a personalização da interface por parte do utilizador, com a gestão de operações e definição de políticas de segurança por parte da organização, de forma independente relativamente ao sistema de informação subjacente.

Rede social de leitores e escritores juniores: portal Biblon: a integração social on-line como catalisador da leitura, criação, expressão e partilha

Com enquadramento nas áreas de Ciência da Informação, Tecnologias de Informação e Comunicação e Educação, o estudo em voga visa formular propostas para o uso de rede social on-line de literatura infantil, em torno da biblioteca, para a educação básica, fundamentadas na teoria de comunidades de prática. O estudo de caso recaiu sobre quatro escolas, do 1º ciclo, da Educação Básica, do Agrupamento de Escolas de Aveiro-Portugal, tendo como instrumento para o experimento o Portal Biblon. A análise dos dados permite afirmar que a leitura de livros on-line não está inclusa nas atividades habituais da comunidade escolar pesquisada e, assim, o aluno encontra-se sem referencial para inserir esta prática cultural em suas rotinas e momentos de ócio. O cenário escolar atual não estimula a confluências da prática da leitura literária e da escrita dos alunos com as redes sociais on-line. O estudo aponta que, em uma rede social on-line, o livro de literatura infantil tem o papel de interagente, agregando leitores, em interação, em torno de si e que nas redes sociais on-line tem-se a presença dos “mediadores sociais centrais” que propiciam reforço e sustentação das práticas de leitura, através do contágio e da influência social e são propulsionadores da estrutura e do dinamismo da rede. Como conclusão geral tem-se que os utilizadores do Biblon desenvolvem experiências de leituras e escritas através da interação social, por meio de práticas, rotinas, diálogos e atividades comuns construídas na rede. A interação dentro da rede influencia o uso das ferramentas e o aprendizado para manuseá-las ocorre com as práticas. Assim, os laços associativos e as reações individuais envolvendo a leitura conduzem à formação de rede social em torno dos livros e os comportamentos e as preferências dos atores motivam a leitura e a escrita. Dessa forma, o Portal Biblon configura-se como um instrumento para formação de rede social on-line em torno da literatura infantil.

Portal de apoio à matemática

Trabalho de projeto de mestrado, Educação (Especialidade de Educação e Tecnologias Digitais), Universidade de Lisboa, Instituto de Educação, 2014