Discovering lesser known molecular players and mechanistic patterns in Alzheimer's disease using an integrative disease modelling approach

Convergence of exponentially advancing technologies is driving medical research with life changing discoveries. On the contrary, repeated failures of high-profile drugs to battle Alzheimer's disease (AD) has made it one of the least successful therapeutic area. This failure pattern has provoked researchers to grapple with their beliefs about Alzheimer's aetiology. Thus, growing realisation that Amyloid-β and tau are not 'the' but rather 'one of the' factors necessitates the reassessment of pre-existing data to add new perspectives. To enable a holistic view of the disease, integrative modelling approaches are emerging as a powerful technique. Combining data at different scales and modes could considerably increase the predictive power of the integrative model by filling biological knowledge gaps. However, the reliability of the derived hypotheses largely depends on the completeness, quality, consistency, and context-specificity of the data. Thus, there is a need for agile methods and approaches that efficiently interrogate and utilise existing public data. This thesis presents the development of novel approaches and methods that address intrinsic issues of data integration and analysis in AD research. It aims to prioritise lesser-known AD candidates using highly curated and precise knowledge derived from integrated data. Here much of the emphasis is put on quality, reliability, and context-specificity. This thesis work showcases the benefit of integrating well-curated and disease-specific heterogeneous data in a semantic web-based framework for mining actionable knowledge. Furthermore, it introduces to the challenges encountered while harvesting information from literature and transcriptomic resources. State-of-the-art text-mining methodology is developed to extract miRNAs and its regulatory role in diseases and genes from the biomedical literature. To enable meta-analysis of biologically related transcriptomic data, a highly-curated metadata database has been developed, which explicates annotations specific to human and animal models. Finally, to corroborate common mechanistic patterns — embedded with novel candidates — across large-scale AD transcriptomic data, a new approach to generate gene regulatory networks has been developed. The work presented here has demonstrated its capability in identifying testable mechanistic hypotheses containing previously unknown or emerging knowledge from public data in two major publicly funded projects for Alzheimer's, Parkinson's and Epilepsy diseases

Training of Crisis Mappers and Map Production from Multi-sensor Data: Vernazza Case Study (Cinque Terre National Park, Italy)

This aim of paper is to presents the development of a multidisciplinary project carried out by the cooperation between Politecnico di Torino and ITHACA (Information Technology for Humanitarian Assistance, Cooperation and Action). The goal of the project was the training in geospatial data acquiring and processing for students attending Architecture and Engineering Courses, in order to start up a team of "volunteer mappers". Indeed, the project is aimed to document the environmental and built heritage subject to disaster; the purpose is to improve the capabilities of the actors involved in the activities connected in geospatial data collection, integration and sharing. The proposed area for testing the training activities is the Cinque Terre National Park, registered in the World Heritage List since 1997. The area was affected by flood on the 25th of October 2011. According to other international experiences, the group is expected to be active after emergencies in order to upgrade maps, using data acquired by typical geomatic methods and techniques such as terrestrial and aerial Lidar, close-range and aerial photogrammetry, topographic and GNSS instruments etc.; or by non conventional systems and instruments such us UAV, mobile mapping etc. The ultimate goal is to implement a WebGIS platform to share all the data collected with local authorities and the Civil Protectio

5W+1H pattern: A perspective of systematic mapping studies and a case study on cloud software testing

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Prevention of mother-to-child-transmission of HIV in Khayelitsha: a contemporary review of services 20 years later

Background: It's been 20 years since the Western Cape (WC) province of South Africa launched its first Prevention of Mother-To-Child-Transmission of HIV(PMTCT) pilot programme in Khayelitsha. The programme evolved alongside the World Health Organization (WHO) guidelines; in 2013 the recommended guidelines in the province was WHO Option B+( life-long antiretroviral therapy (ART) irrespective of CD4 count, and exclusive breastfeeding for the first 6 months of life). Alongside the explanation of the PMTCT programme, the province gradually implemented patient administrative systems in all fixed public health facilities; these systems all shared a unique patient identifier called the folder number. The digitization of folder number lead to the establishment of the Provincial Health Data Centre (PHDC), an African health information exchange (HIE) developed and hosted in the WC Department of Health. The HIE also integrated data from disease management information systems (Three Interlinked Electronic Registers (TIER) and the Electronic Tuberculosis Register (ETR)), allowing the ability to track the cohort of pregnant women living with HIV who attend public health services across the Western Cape. Here we report the latest analysis of vertical HIV transmission in the era of WHO Option B+ with the advantage of a maturing consolidated African HIE. The primary aim of the study was to describe coverage of the PMTCT care cascade, including the implementation of maternal viral load monitoring and early infant diagnosis, among HIV positive women who presented antenatal care, or delivered in the absence of antenatal care, at a public health facility in Khayelitsha subdistrict in 2017; and to quantify MTCT risk factors and outcomes among this cohort up to 12 months post-partum. Methods: Patient-level consolidated PHDC data were used to draw an observational cohort consisting of all live-born and linked mother-infant pairs in which the mother was HIV positive, at any point prior to her first antenatal visit up to 12 months post-partum and attended antenatal care, or in the absence of antenatal care delivered in Khayelitsha in 2017. The PHDC provided a single summative record per pregnancy for each woman (linked to her infant after birth) which enabled the assessment of PMTCT uptake from her first antenatal visit through delivery to infant early infant diagnosis (EID) of HIV-PCR testing and PHDC ascertainment of HIV up to the end of the index period (i.e. 12 months post-partum). iii Using this cohort of HIV-exposed infants, a protocol was designed (Section A: Protocol) to assess the outcomes of the implementation of WHO Option B+(lifelong ART for all HIV positive pregnant women; and periodic re-testing of HIV negative women) under the latest EID guidelines of routine birth HIV-PCR (within 1 week of birth), and repeat testing at 10 weeks (between 2 and 14 weeks of birth) or a first HIV-test at 10 weeks if the infant had not been tested at birth. Continuous variables were converted to categorical variables according to pre-set thresholds, all categorical variables were described using proportions, and frequency tables were used for comparison. Timing of ART initiation was categorized as a binary variable which was assigned 1 if the mother started ART before the first antenatal visits, and 0 of she started ART at the first antenatal visit or anytime during the pregnancy. Viral load was categorised according to coverage and suppression status; virologic suppression was defined as having a viral load of 1000 copies/ml or less after 3 months on ART. Analysis was performed in using R studio; descriptive statistics were used to assess coverage along the PMTCT care cascade, and logistic regression was run to quantify a priori defined risk factors associated with MTCT. Results: The study cohort of 2 576 mother-infant pairs (2548 women living with HIV (WLHIV)) presented in the manuscript was a young cohort with a median age of 30 years (interquartile range of 26 – 34), in which most women delivered vaginally (70.5%), and 78.3% attended at least one antenatal visit before delivery. Most WLHIV (88.3%) presented to their first pregnancy related visit (antenatal care or delivery) already knowing their status, of whom 77.9% were already on ART. 94.5% of women diagnosed prior to birth were initiated on ART prior; 85.0% of these women received a viral load test antenatally, of whom 88.0% were virologically suppressed. Early infant diagnosis coverage was sub-optimal with birth HIV-PCR (within 7 days of birth) coverage of 79.21% among HIV exposed infants (HEI); an even lower proportion (57.9%) of HEI who tested negative at birth had a repeat test around 10-weeks. HIV-PCR ascertained MTCT was 0.8% at 10 weeks, consolidated data from the PHDC suggested an MTCT of 1.8% by the end of the index period (the PHDC HIV episode identified an additional 16 HIVexposed (HEI) infants with HIV who were not detected by laboratory tests). PWLHIV who started ART prior to the first antenatal visit had 50% reduced risk of MTCT compared to those who started ART during the pregnancy. Women who were not suppressed antenatally had a 5- fold (aOR = 5.3, 95% CI: 2.5 – 12.3) increased MTCT risk compared to those were suppressed antenatally. Women who did not attend ANC were at highest risk of transmission (aOR=1.6,95%CI: 0.7 – 3.6). iv Conclusion: Although women most women present to care already knowing their HIV status, ART initiation and uptake of viral load testing is very low at presentation but improved significantly during pregnancy, evidence of maturing PMCT services. National and Provincial MTCT is likely to be underestimated as it relies solely on PCR results; the uptake of the birth PCR among HIV-exposed infants is still not 100% (where it should be) and the uptake of a repeat tests among infants that tested negative is even lower. PHDC data, which consolidates HIV data from multiple sources, revealed a higher MTCT than HIV-PCR testing alone

ADAPT: Approach to Develop context-Aware solutions for Personalised asthma managemenT

The creation of sensors allowing the collection of a high amount of data has been possible thanks to the evolution of information and communication technology. These data must be properly interpreted to deliver meaningful information and services. Context-aware reasoning plays an important role in this task, and it is considered as a hot topic to study in the development of solutions that can be categorised under the scope of Intelligent Environments. This research work studies the use of context-aware reasoning as a tool to provide support in the asthma management process. The contribution of this study is presented as the Approach to Develop context-Aware solutions for Personalised asthma managemenT (ADAPT), which can be used as a guideline to create solutions supporting asthma management in a personalised way. ADAPT proposes context-aware reasoning as an appropriate tool to achieve the personalisation that is required to address the heterogeneity of asthma. This heterogeneity makes people with asthma have different triggers provoking their exacerbations and to experience different symptoms when their exacerbations occur, which is considered as the most challenging characteristic of the condition when it comes to implementing asthma treatments. ADAPT context dimensions are the main contribution of the research work as they directly address the heterogeneity of asthma management by allowing the development of preventive and reactive features that can be customised depending on the characteristics of a person with asthma. The approach also provides support to people not knowing their triggers properly through case-based reasoning, and includes virtual assistant as a complementing technology supporting asthma management. The comprehensive nature of ADAPT motivates the study of the interaction between context-aware reasoning and case-based reasoning in Intelligent Environments, which is also reported as a key contribution of the research work. The inclusion of people with asthma, carers and experts in respiratory conditions in the experiments of the research project was possible to achieve thanks to the collaboration formed with Asthma UK

DevOps practices in incident management process

This research aims to investigate how DevOps culture can be applied in the incident management process to improve it. Given the exploratory approach of the research, it was performed a case study. For this case study an application management team was studied where a sample of 10 persons were interviewed. This team solves incidents and provides the necessary support to the users in their daily business tasks using DevOps practices. During this case study three data collection methods were used: semi structured interviews, document analysis and observation. This research provides novel findings about a possible relation between DevOps practices and incident management phases as well as on “why” and “how” can these practices help incident management. The results are supported by metrics, like time between releases, total of over delivered incidents solutions and releases per month, to justify how this team’s performance have increased after the implementation of DevOps practices. The novelty of the findings brings advantages for academics, and due to the exploratory nature of this research, it extends the body of knowledge. It also provides contributions for practitioners, by showing how these practices can be applied and the result of the implementation of these practices. Directions of future work are also presented.O objetivo desta pesquisa é investigar como a cultura DevOps pode ser aplicada ao processo de gestão de incidentes e como pode melhorá-lo. Dada a abordagem exploratória para esta pesquisa, foi feito um caso de estudo. O objeto de estudo para esta pesquisa, foi uma equipa de gestão aplicacional em gestão de incidentes, onde um conjunto de 10 pessoas foi entrevistado. Esta equipa resolve incidentes e fornece o suporte necessário aos utilizadores de negócio, nas suas tarefas do dia a dia, utilizando práticas DevOps. Durante a elaboração deste caso de estudo, foi feita a triangulação de três métodos de recolha de dados: entrevistas semiestruturadas, análise documental e observação. Esta pesquisa fornece novas conclusões sobre uma possível relação entre práticas de DevOps e as fases do processo de gestão de incidentes, tal como o “porquê” e o “como” estas práticas podem ajudar o processo de gestão de incidentes. São apresentados resultados, como o tempo entre entregas, total de soluções de incidentes entregues a mais do que estava planeado e o número de entregas por mês, de forma a justificar como existiu uma melhoria de desempenho desta equipa após a implementação destas práticas. As conclusões que são apresentadas nesta pesquisa trazem vantagens tanto para académicos devido à natureza exploratória deste estudo que estende o corpo de conhecimento científico. E também para profissionais, por demonstrar como aplicar estas práticas e os seus resultados após implementação. Direções para trabalho futuro são também apresentadas