Helena Sofia Rodrigues

Importance of TP53 codon 72 and intron 3 duplication 16bp polymorphisms in prediction of susceptibility on breast cancer

BackgroundTP53 is one of major tumour suppressor genes being essential in preservation of genome integrity. Two very common polymorphisms have been demonstrated to contribute to cancer susceptibility and tumour behaviour. The purpose of this study was to evaluate the role of Arg72Pro and PIN3 Ins16bp polymorphisms in TP53 gene as genetic susceptibility and predictive markers to breast cancer.MethodsWe analysed DNA samples from 264 breast cancer patients and 440 controls, for TP53 Arg72Pro and PIN3 Ins16bp polymorphisms using PCR-RFLP.ResultsWe observed that women with A2A2 genotype have increased risk for developing breast cancer, either in women with or without familial history (FH) of the disease (OR = 4.40, 95% CI 1.60–12.0; p = 0.004; OR = 3.88, 95% CI 1.18–12.8; p = 0.026, respectively). In haplotype analysis, statistically significant differences were found between TP53 Arg-A2 haplotype frequencies and familial breast cancer cases and the respective control group (OR = 2.10, 95% CI 1.08–4.06; p = 0.028). Furthermore, both TP53 polymorphisms are associated with higher incidence of lymph node metastases.ConclusionOur findings suggest TP53 PIN3 Ins16bp polymorphism as a real risk modifier in breast cancer disease, either in sporadic and familial breast cancer. Furthermore, both TP53 polymorphisms are associated with higher incidence of lymph node metastases.

Quantification of Free Circulating Tumor DNA as a Diagnostic Marker for Breast Cancer

AIM To determine whether the amounts of circulating DNA could discriminate between breast cancer patients and healthy individuals by using real-time PCR quantification methodology. METHODS Our standard protocol for quantification of cell-free plasma DNA involved 175 consecutive patients with breast cancer and 80 healthy controls. RESULTS We found increased levels of circulating DNA in breast cancer patients compared to control individuals (105.2 vs. 77.06 ng/mL, p < 0.001). We also found statistically significant differences in circulating DNA amounts in patients before and after breast surgery (105.2 vs. 59.0 ng/mL, p = 0.001). Increased plasma cell-free DNA concentration was a strong risk factor for breast cancer, conferring an increased risk for the presence of this disease (OR, 12.32; 95% CI, 2.09-52.28; p < 0.001). CONCLUSIONS Quantification of circulating DNA by real-time PCR may be a good and simple tool for detection of breast cancer with a potential to clinical applicability together with other current methods used for monitoring the disease.

Vaccination models and optimal control strategies to dengue

As the development of a dengue vaccine is ongoing, we simulate an hypothetical vaccine as an extra protection to the population. In a first phase, the vaccination process is studied as a new compartment in the model, and different ways of distributing the vaccines investigated: pediatric and random mass vaccines, with distinct levels of efficacy and durability. In a second step, the vaccination is seen as a control variable in the epidemiological process. In both cases, epidemic and endemic scenarios are included in order to analyze distinct outbreak realities.

Dengue disease, basic reproduction number and control

Dengue is one of the major international public health concerns. Although progress is underway, developing a vaccine against the disease is challenging. Thus, the main approach to fight the disease is vector control. A model for the transmission of dengue disease is presented. It consists of eight mutually exclusive compartments representing the human and vector dynamics. It also includes a control parameter (insecticide) in order to fight the mosquito. The model presents three possible equilibria: two disease-free equilibria (DFE) and another endemic equilibrium. It has been proved that a DFE is locally asymptotically stable, whenever a certain epidemiological threshold, known as the basic reproduction number, is less than one. We show that if we apply a minimum level of insecticide, it is possible to maintain the basic reproduction number below unity. A case study, using data of the outbreak that occurred in 2009 in Cape Verde, is presented.

Ambient Intelligence: Beyond the Inspiring Vision.

Ambient Intelligence (AmI) has emerged in the past 10 years as a multidisciplinary field within ubiquitous computing, attracting considerable research, funding and public attention and leading to many research groups, and conferences specifically focused on Ambient Intelligence topics. From its conception, AmI has always been a field strongly driven by a particular vision of how ICT technologies would shape our future. This has given the AmI vision, essentially as proposed by ISTAG, an excessively central role in shaping the field and setting its research agenda. We argue that this inspiring vision should no longer be the main driver for AmI research and that we should now re-interpret its role in the background of 10 years of research. In this paper, we reflect on what it means for AmI to move behind its foundational vision and we identify a number of emerging trends around some of its core concepts, more specifically the notion of intelligence, the system view and the requirements process. The main motivation is to search for alternative research directions that may be more effective in delivering today the essence of the AmI vision, even if they mean abandoning some of the currently prevailing approaches and assumptions. Overall, these trends provide a more holistic view of AmI and may represent important contributions for bringing this field closer to realisation, delivery and real social impact.

The c.156_157insAlu BRCA2 rearrangement accounts for more than one-fourth of deleterious BRCA mutations in northern/central Portugal

We evaluated the contribution of an Alu insertion in BRCA2 exon 3 (c.156_157insAlu) to inherited predisposition to breast/ovarian cancer in 208 families originated mostly from northern/central Portugal. We identified the c.156_157insAlu BRCA2 mutation in 14 families and showed that it accounts for more that one-fourth of deleterious BRCA1/BRCA2 mutations in breast/ovarian cancer families originated from this part of the country. This mutation originates BRCA2 exon 3 skipping and we demonstrated its pathogenic effect by showing that the BRCA2 full length transcript is derived only from the wild type allele in carriers, that it is absent in 262 chromosomes from healthy blood donors, and that it co-segregates with the disease. Polymorphic microsatellite markers were used for haplotype analysis in three informative families. In two of the three families one haplotype was shared for all but two markers, whereas in the third family all markers telomeric to BRCA2 differed from that observed in the other two. Although the c.156_157insAlu BRCA2 mutation has so far only been identified in Portuguese breast/ovarian cancer families, screening of this rearrangement in other populations will allow evaluation of whether or not it is a population-specific founder mutation and a more accurate estimation of its distribution and age.

Dynamics of Dengue epidemics when using optimal control

We present an application of optimal control theory to Dengue epidemics. This epidemiologic disease is important in tropical countries due to the growing number of infected individuals. The dynamic model is described by a set of nonlinear ordinary differential equations, that depend on the dynamics of the Dengue mosquito, the number of infected individuals, and peoples motivation to combat the mosquito. The cost functional depends not only on the costs of medical treatment of the infected people but also on the costs related to educational and sanitation campaigns. Two approaches for solving the problem are considered: one using optimal control theory, the other carried out by first discretizing the problem and then solving it with nonlinear programming. The results obtained with OC-ODE and IPOPT solvers are given and discussed. We observe that with current computational tools it is easy to obtain, in an efficient way, better solutions to Dengue problems, leading to a decrease in the number of infected mosquitoes and individuals in less time and with lower costs.

Fractional Derivatives in Dengue Epidemics

We introduce the use of fractional calculus, i.e., the use of integrals and derivatives of non‐integer (arbitrary) order, in epidemiology. The proposed approach is illustrated with an outbreak of dengue disease, which is motivated by the first dengue epidemic ever recorded in the Cape Verde islands off the coast of west Africa, in 2009. Numerical simulations show that in some cases the fractional models fit better the reality when compared with the standard differential models. The classical results are obtained as particular cases by considering the order of the derivatives to take an integer value.

Dengue in Cape Verde: vector control and vaccination

In 2009, for the first time in Cape Verde, an outbreak of dengue was reported and more than 20,000 people were infected. Only a few prophylactic measures were taken. The effects of vector control on disease spreading, such as insecticide (larvicide and adulticide) and mechanical control, as well as an hypothetical vaccine, are estimated through simulations with the Cape Verde data.

Beyond interaction: tools and practices for situated publication in display networks

The ability to engage users in content generation is both a major goal and a major challenge for public displays. While previous work has extensively explored the specific challenges associated with interaction processes, little attention has been paid to the broad range of issues that go beyond interaction itself. More specifically, public display systems do not seem to offer a set of tools and techniques that people may feel comfortable to use for whatever communication purposes they might have. There are no publication concepts that can frame expectations on how content creation, distribution, presentation and curation are handled by display systems. In our research, we seek to explore new publication concepts for public displays, and for that purpose we have developed instant places, a platform enabling people to connect with the places they visit and control the projection of their identity in public displays. The system frames interaction events within two specific publication concepts: pin badges and posters. We describe our first deployments at three different locations and the results obtained from usage data and in-situ surveys about content publication practices.