Importance in the acquisition of the transversal competences in the degree of law

This project aims to clarify the importance of acquiring cross-disciplinary competencies in the Law and Criminology degrees, specifically entrepreneurial capability in order to further students' comprehensive training and complete preparation for the legal and professional sector, thereby fostering students' greater involvement in the development of such competencies.

Teaching / learning process through the case method in the law degree

This project in teaching innovation and improvement aims to disseminate the case method as one of the most innovative educational instruments inteaching of Law in general, and specifically with regard to Family and Inheritance Law. The methodology used ensures learning through a legal conflict, which must be resolved by the students themselves from different viewpoints as legal agents. This is an activity in teaching innovation, in which students become the protagonists. Participation is voluntary, and the main aim is student motivation. The subject's aim is for students to learn public speaking skills fundamental to the profession while familiarising themselves with judicial practice. Theteacher sets up a legal conflict in order for students to resolve the dispute as legal agents with divergent viewpoints - in other words, as judges, attorneys, lawyers and so on. The project seeks alternatives to traditional teaching methods and is an innovative teaching method aimed at professionally training future lawyers as well as being a model that involves students more in their own learning.

The role of cancer related inflammation, Src family kinases and matrix metalloproteinase 9 in colorectal cancer

Colorectal cancer (CRC) is the third most common cancer in the UK with 41,000 new cases diagnosed in 2011. Despite undergoing potentially curative resection, a significant amount of patients develop recurrence. Biomarkers that aid prognostication or identify patients who are suitable for adjuvant treatments are needed. The TNM staging system does a reasonably good job at offering prognostic information to the treating clinician, but it could be better and identifying methods of improving its accuracy are needed. Tumour progression is based on a complex relationship between tumour behaviour and the hosts’ inflammatory responses. Sustained tumour cell proliferation, evading growth suppressors, resisting apoptosis, replicative immortality, sustained angiogenesis, invasion & metastasis, avoiding immune destruction, deregulated cellular energetics, tumour promoting inflammation and genomic instability & mutation have been identified as hallmarks. These hallmarks are malignant behaviors are what makes the cell cancerous and the more extreme the behaviour the more aggressive the cancer the more likely the risk of a poor outcome. There are two primary genomic instability pathways: Microsatellite Instability (MSI) and Chromosomal Instability (CI) also referred to as Microsatellite Stability (MSS). Tumours arising by these pathways have a predilection for specific anatomical, histological and molecular biological features. It is possible that aberrant molecular expression of genes/proteins that promote malignant behaviors may also act as prognostic and predictive biomarkers, which may offer superior prognostic information to classical prognostic features. Cancer related inflammation has been described as a 7th hallmark of cancer. Despite the systemic inflammatory response (SIR) being associated with more aggressive malignant disease, infiltration by immune cells, particularly CD8+ lymphocytes, at the advancing edge of the tumour have been associated with improved outcome and tumour MSI. It remains unknown if the SIR is associated with tumour MSI and this requires further study. The mechanisms by which colorectal cancer cells locally invade through the bowel remain uncertain, but connective tissue degradation by matrix metalloproteinases (MMPs) such as MMP-9 have been implicated. MMP-9 has been found in the cancer cells, stromal cells and patient circulation. Although tumoural MMP-9 has been associated with poor survival, reports are conflicting and contain relatively small sample sizes. Furthermore, the influence of high serum MMP-9 on survival remains unknown. Src family kinases (SFKs) have been implicated in many adverse cancer cell behaviors. SFKs comprise 9 family members BLK, C-SRC, FGR, FYN, HCK, LCK, LYN, YES, YRK. C-SRC has been the most investigated of all SFKs, but the role of other SFKs in cellular behaviors and their prognostic value remains largely unknown. The development of Src inhibitors, such as Dasatinib, has identified SFKs as a potential therapeutic target for patients at higher risk of poor survival. Unfortunately, clinical trials so far have not been promising but this may reflect inadequate patient selection and SFKs may act as useful prognostic and predictive biomarkers. In chapter 3, the association between cancer related inflammation, tumour MSI, clinicopathological factors and survival was tested in two independent cohorts. A training cohort consisting of n=182 patients and a validation cohort of n=677 patients. MSI tumours were associated with a raised CRP (p=0.003). Hypoalbuminaemia was independently associated with poor overall survival in TNM stage II cancer (HR 3.04 (95% CI 1.44 – 6.43);p=0.004), poor recurrence free survival in TNM stage III cancer (HR 1.86 (95% 1.03 – 3.36);p=0.040) and poor overall survival in CI colorectal cancer (HR 1.49 (95% CI 1.06 – 2.10);p=0.022). Interestingly, MSI tumours were associated with poor overall survival in TNM stage III cancer (HR 2.20 (95% CI 1.10 – 4.37);p=0.025). In chapter 4, the role of MMP-9 in colorectal cancer progression and survival was examined. MMP-9 in the tissue was assessed using IHC and serum expression quantified using ELISA. Serum MMP-9 was associated with cancer cell expression (Spearman’s Correlation Coefficient (SCC) 0.393, p<0.001)) and stromal expression (SCC 0.319, p=0.002). Serum MMP-9 was associated with poor recurrence-free (HR 3.37 (95% CI 1.20 – 9.48);p=0.021) and overall survival (HR 3.16 (95% CI 1.22 – 8.15);p=0.018), but tumour MMP-9 was not survival or MSI status. In chapter 5, the role of SFK expression and activation in colorectal cancer progression and survival was studied. On PCR analysis, although LYN, C-SRC and YES were the most highly expressed, FGR and HCK had higher expression profiles as tumours progressed. Using IHC, raised cytoplasmic FAK (tyr 861) was independently associated with poor recurrence free survival in all cancers (HR 1.48 (95% CI 1.02 – 2.16);p=0.040) and CI cancers (HR 1.50 (95% CI 1.02 – 2.21);p=0.040). However, raised cytoplasmic HCK (HR 2.04 (95% CI 1.11 – 3.76);p=0.022) was independently associated with poor recurrence-free survival in TNM stage II cancers. T84 and HT29 cell lines were used to examine the cellular effects of Dasatinib. Cell viability was assessed using WST-1 assay and apoptosis assessed using an ELISA cell death detection assay. Dasatinib increased T84 tumour cell apoptosis in a dose dependent manner and resulted in reduced expression of nuclear (p=0.008) and cytoplasmic (p=0.016) FAK (tyr 861) expression and increased nuclear FGR expression (p=0.004). The results of this thesis confirm that colorectal cancer is a complex disease that represents several subtypes of cancer based on molecular biological behaviors. This thesis concentrated on features of the disease related to inflammation in terms of genetic and molecular characterisation. MSI cancers are closely associated with systemic inflammation but despite this observation, they retain their relatively improved survival. MMP-9 is a feature of tissue remodeling during inflammation and is also associated with degradation of connective tissue, advanced T-stage and poor outcome when measured in the serum. The lack of stromal quantification due to TMA use rather than full sections makes the value of tumoural MMP-9 immunoreactivity in the prognostication and its association with MSI unknown and requires further study. Finally, SFK activation was also associated with SIR, however, only cytoplasmic HCK was independently associated with poor survival in patients with TNM stage II disease, the group of patients where identifying a novel biomarker is most needed. There is still some way to go before these biomarkers are translated into clinical practice and future work needs to focus on obtaining a reliable and robust scientific technique with validation in an adequately powered independent cohort.

Stable isotope and multi-analytical investigation of Monte da Cegonha: A Late Antiquity population in southern Portugal

This study presents for the first time the diet of a Late Antiquity population in southern Portugal (Civitas of Pax Julia), from the Roman villa of Monte da Cegonha (predominantly 7th century CE). Stable isotope analysis (δ13C, δ15N, δ18O, 87Sr/86Sr) of human and faunal bone collagen and apatite was conducted in order to understand the influence of Roman subsistence strategies on the way of life of rural inhabitants of the area of Pax Julia and to explore their diet (types of ingested plants, amount of animal resources, terrestrial versus marine resources). X-ray diffraction (XRD) and Fourier transform infra-red spectroscopy (FTIR) analyses were used to determine the degree of bone diagenesis and assess the reliability of the bone stable isotopic composition for palaeodietary reconstruction. Anthropological analysis revealed a cariogenic diet, rich in starchy food and carbohydrates, in at least in two individuals based on the frequency of dental caries. Collagen and apatite carbon isotopic analysis suggested that C3 plants were the basis of the population's diet, complemented with some terrestrial meat and its by-products as reflected by the observed bone collagen nitrogen isotopic composition. Moreover, whilst the fairly low apatite-collagen spacing recorded in some skeletons (at around 4‰) may have been due to freshwater organisms intake, the relatively low nitrogen values observed indicate that this consumption did not occur very often, unless in the form of fresh fish of low trophic level or fish sauces. There were no significant differences in isotopic values depending on gender or burial type. Strontium and oxygen isotopic composition of bone apatite revealed a sedentary community, with the exception of a male individual who probably did not spend his childhood in Monte da Cegonha.

Proposal for Labor Market Integration of Teachers in Contexts of High Social Vulnerability

The purpose of this paper is to share a proposal for teacher’s labor market integration in contexts of high social5 vulnerability. This paper is the result of a research conducted in a priority attention primary school6 of the central canton of Heredia7. It explored the labor market integration process of teachers, considering the community, family and student reality of a population social risk. The research that supports this proposal is based on a qualitative approach, since the diagnosis process is not intended to provide answers that could be commonly applied to other education centers in similar contexts, but to make an exploratory approach of teachers’ reality and their integration process into education institutions of high social vulnerability. Therefore, although this paper intends to share this experience, it does not aim to unify integration practices, but to be an input in carrying out similar processes.  (5) The concept of high social vulnerability is understood based on Sojo’s approach (2003), which defines it as marginal urban communities in areas considered by the Costa Rican government as priority areas with the greatest social, economic backwardness in the country, and high rates of violence, leisure, unemployment and drug addiction. (6) Translator’s note: The Costa Rican education system is composed of primary education (1st-6th grade) and secondary education (7th-11th grade). (7)A public primary school in the circuit 02 of the Province of Heredia.

Competencies Required in Education Research and Teaching Systematization according to Students from the Preschool, Primary and Secondary Education Programs of the University of Costa Rica

The purpose of this paper is to present the results of two online forums carried out with the participation of 42 students of the Licenciaturas  in Preschool Education, Primary Education and Secondary Education of the University of Costa Rica. The main purpose of the forums was to determine the insights of the participant students about the competencies they have achieved in the field of education research, and which have been the essential tools for them to systematize their own teaching practices. The discussion forums were part of the course FD5091 Métodos de Investigación Educativa [Education Research Methods] of the School of Teacher Education, delivered from March-April 2010.  Of the sample, 60 percent were students of the Preschool teaching program, 35 percent were from the Primary Education teaching program and 5 percent were from the Secondary Education teaching program in the fields of Science, Mathematics and Social Studies. According to the insights and beliefs showed by the participants –both, the future teachers and the profession practitioners–, there are no opportunities for research or systematization of their own teaching mediation, in the current work situation.(1) Translator’s Note: In Costa Rica, the “Licenciatura” is a one-year post-Bachelor study program, usually including thesis. “Primary Education” refers to students from the 1st to 6th grades, and “Secondary Education” refers to students from the 7th to 11th grades.

Patterns of long-term settlement and land exploitation in the region of the Nile First Cataract (Egypt)

The First Cataract region (Egypt) has always played a crucial role as a border area and a crossroads for cultures and people living in adjacent landscapes. The region has its central point in the modern city of Aswan, but it extends up to the Kom Ombo Plain in the north and reaches the Bab el-Kalabsha in the south. Its eastern and western limits cannot be defined with the same precision, given that they are located in deserts. This research focused on the landscape analysis of the region intended as a complex entanglement of archaeological evidence in a geographical and natural environment whose changes impacted and, simultaneously, were influenced by human activities. Settlement patterns and land use can give interesting information on how these relationships worked from a diachronic perspective and how they shaped the region’s characteristics. To understand the links between the human presence and its evidence and the landscape of the First Cataract region, the integration of various datasets was needed, from historical and archaeological ones to the remote sensing observation of large areas. An area corresponding to ca. 18.000 km2 has been selected for this research. The chronological framework has been chosen to cover a considerable period, from the beginning of the 5th millennium BCE to the 7th century AD. Multi-temporality and multifunctionality appear as two essential aspects when the archaeological evidence of the First Cataract region is considered in its geographical and topographical setting as a general context for settlement patterns and resource exploitation analyses. A combination of remote sensing data and topographical materials has been integrated with archaeological evidence to obtain information about resource exploitation strategies and settlement adaptation from a diachronic perspective.

Pipkiiα Is Widely Expressed In Hematopoietic-derived Cells And May Play A Role In The Expression Of Alpha- And Gamma-globins In K562 Cells.

Characterized for the first time in erythrocytes, phosphatidylinositol phosphate kinases (PIP kinases) belong to a family of enzymes that generate various lipid messengers and participate in several cellular processes, including gene expression regulation. Recently, the PIPKIIα gene was found to be differentially expressed in reticulocytes from two siblings with hemoglobin H disease, suggesting a possible relationship between PIPKIIα and the production of globins. Here, we investigated PIPKIIα gene and protein expression and protein localization in hematopoietic-derived cells during their differentiation, and the effects of PIPKIIα silencing on K562 cells. PIPKIIα silencing resulted in an increase in α and γ globins and a decrease in the proliferation of K562 cells without affecting cell cycle progression and apoptosis. In conclusion, using a cell line model, we showed that PIPKIIα is widely expressed in hematopoietic-derived cells, is localized in their cytoplasm and nucleus, and is upregulated during erythroid differentiation. We also showed that PIPKIIα silencing can induce α and γ globin expression and decrease cell proliferation in K562 cells.

The Clinical Impact Of Cerebellar Grey Matter Pathology In Multiple Sclerosis.

The cerebellum is an important site for cortical demyelination in multiple sclerosis, but the functional significance of this finding is not fully understood. To evaluate the clinical and cognitive impact of cerebellar grey-matter pathology in multiple sclerosis patients. Forty-two relapsing-remitting multiple sclerosis patients and 30 controls underwent clinical assessment including the Multiple Sclerosis Functional Composite, Expanded Disability Status Scale (EDSS) and cerebellar functional system (FS) score, and cognitive evaluation, including the Paced Auditory Serial Addition Test (PASAT) and the Symbol-Digit Modalities Test (SDMT). Magnetic resonance imaging was performed with a 3T scanner and variables of interest were: brain white-matter and cortical lesion load, cerebellar intracortical and leukocortical lesion volumes, and brain cortical and cerebellar white-matter and grey-matter volumes. After multivariate analysis high burden of cerebellar intracortical lesions was the only predictor for the EDSS (p<0.001), cerebellar FS (p = 0.002), arm function (p = 0.049), and for leg function (p<0.001). Patients with high burden of cerebellar leukocortical lesions had lower PASAT scores (p = 0.013), while patients with greater volumes of cerebellar intracortical lesions had worse SDMT scores (p = 0.015). Cerebellar grey-matter pathology is widely present and contributes to clinical dysfunction in relapsing-remitting multiple sclerosis patients, independently of brain grey-matter damage.

Antiangiogenic And Finasteride Therapies: Responses Of The Prostate Microenvironment In Elderly Mice.

The aim of this study was to evaluate the structural and molecular effects of antiangiogenic therapies and finasteride on the ventral prostate of senile mice. 90 male FVB mice were divided into: Young (18 weeks old) and senile (52 weeks old) groups; finasteride group: finasteride (20mg/kg); SU5416 group: SU5416 (6 mg/kg); TNP-470 group: TNP-470 (15 mg/kg,) and SU5416+TNP-470 group: similar to the SU5416 and TNP-470 groups. After 21 days, prostate ventral lobes were collected for morphological, immunohistochemical and Western blotting analyses. The results demonstrated atrophy, occasional proliferative lesions and inflammatory cells in the prostate during senescence, which were interrupted and/or blocked by treatment with antiangiogenic drugs and finasteride. Decreased AR and endostatin reactivities, and an increase for ER-α, ER-β and VEGF, were seen in the senile group. Decreased VEGF and ER-α reactivities and increased ER-β reactivity were verified in the finasteride, SU5416 groups and especially in SU5416+TNP-470 group. The TNP-470 group showed reduced AR and ER-β protein levels. The senescence favored the occurrence of structural and/or molecular alterations suggesting the onset of malignant lesions, due to the imbalance in the signaling between the epithelium and stroma. The SU5416+TNP-470 treatment was more effective in maintaining the structural, hormonal and angiogenic factor balance in the prostate during senescence, highlighting the signaling of antiproliferation via ER-β.

Adapting The Sniffin' Sticks Olfactory Test To Diagnose Parkinson's Disease In Estonia.

The aim of the study was to develop a culturally adapted translation of the 12-item smell identification test from Sniffin' Sticks (SS-12) for the Estonian population in order to help diagnose Parkinson's disease (PD). A standard translation of the SS-12 was created and 150 healthy Estonians were questioned about the smells used as response options in the test. Unfamiliar smells were replaced by culturally familiar options. The adapted SS-12 was applied to 70 controls in all age groups, and thereafter to 50 PD patients and 50 age- and sex-matched controls. 14 response options from 48 used in the SS-12 were replaced with familiar smells in an adapted version, in which the mean rate of correct response was 87% (range 73-99) compared to 83% with the literal translation (range 50-98). In PD patients, the average adapted SS-12 score (5.4/12) was significantly lower than in controls (average score 8.9/12), p < 0.0001. A multiple linear regression using the score in the SS-12 as the outcome measure showed that diagnosis and age independently influenced the result of the SS-12. A logistic regression using the SS-12 and age as covariates showed that the SS-12 (but not age) correctly classified 79.0% of subjects into the PD and control category, using a cut-off of <7 gave a sensitivity of 76% and specificity of 86% for the diagnosis of PD. The developed SS-12 cultural adaption is appropriate for testing olfaction in Estonia for the purpose of PD diagnosis.

Migraine Equivalents In Childhood.

Migraine equivalents are a group of periodic and paroxysmal neurologic diseases. Because headache is not a prominent symptom, the diagnosis might be challenging. The objective of the study was to evaluate the frequency and outcome of migraine equivalents. This was a retrospective study. We included benign paroxysmal torticollis of infancy, benign paroxysmal vertigo of infancy, abdominal migraine, cyclic vomiting, aura without migraine, and confusional migraine. We evaluated the frequency of events, treatment, and outcome. Out of 674 children with headache, 38 (5.6%) presented with migraine equivalents. Twenty-one were boys and the mean age was 6.1 years. Fifteen had abdominal migraine, 12 benign paroxysmal vertigo, 5 confusional migraine, 3 aura without migraine, 2 paroxysmal torticollis, and 1 cyclic vomiting. Prophylactic treatment was introduced in 23 patients; 4 lost follow-up and 19 had significant improvement. We conclude that the correct diagnosis of migraine equivalents enables an effective treatment with an excellent outcome.

Egfr Activating Mutations And Their Association With Response To Platinum-doublet Chemotherapy In Brazilian Non-small Cell Lung Cancer Patients.

The aim of the study was to analyze the frequency of epidermal growth factor receptor (EGFR) mutations in Brazilian non-small cell lung cancer patients and to correlate these mutations with response to benefit of platinum-based chemotherapy in non-small cell lung cancer (NSCLC). Our cohort consisted of prospective patients with NSCLCs who received chemotherapy (platinum derivates plus paclitaxel) at the [UNICAMP], Brazil. EGFR exons 18-21 were analyzed in tumor-derived DNA. Fifty patients were included in the study (25 with adenocarcinoma). EGFR mutations were identified in 6/50 (12 %) NSCLCs and in 6/25 (24 %) adenocarcinomas; representing the frequency of EGFR mutations in a mostly self-reported White (82.0 %) southeastern Brazilian population of NSCLCs. Patients with NSCLCs harboring EGFR exon 19 deletions or the exon 21 L858R mutation were found to have a higher chance of response to platinum-paclitaxel (OR 9.67 [95 % CI 1.03-90.41], p = 0.047). We report the frequency of EGFR activating mutations in a typical southeastern Brazilian population with NSCLC, which are similar to that of other countries with Western European ethnicity. EGFR mutations seem to be predictive of a response to platinum-paclitaxel, and additional studies are needed to confirm or refute this relationship.

Lung Age Is Related To Carotid Structural Alterations In Hypertensive Subjects.

Hypertensive patients exhibit higher cardiovascular risk and reduced lung function compared with the general population. Whether this association stems from the coexistence of two highly prevalent diseases or from direct or indirect links of pathophysiological mechanisms is presently unclear. This study investigated the association between lung function and carotid features in non-smoking hypertensive subjects with supposed normal lung function. Hypertensive patients (n = 67) were cross-sectionally evaluated by clinical, hemodynamic, laboratory, and carotid ultrasound analysis. Forced vital capacity, forced expired volume in 1 second and in 6 seconds, and lung age were estimated by spirometry. Subjects with ventilatory abnormalities according to current guidelines were excluded. Regression analysis adjusted for age and prior smoking history showed that lung age and the percentage of predicted spirometric parameters associated with common carotid intima-media thickness, diameter, and stiffness. Further analyses, adjusted for additional potential confounders, revealed that lung age was the spirometric parameter exhibiting the most significant regression coefficients with carotid features. Conversely, plasma C-reactive protein and matrix-metalloproteinases-2/9 levels did not influence this relationship. The present findings point toward lung age as a potential marker of vascular remodeling and indicate that lung and vascular remodeling might share common pathophysiological mechanisms in hypertensive subjects.

An Efficient Protocol For The Generation Of Monocyte Derived Dendritic Cells Using Serum-free Media For Clinical Applications In Post Remission Aml Patients.

Protocols for the generation of dendritic cells (DCs) using serum as a supplementation of culture media leads to reactions due to animal proteins and disease transmissions. Several types of serum-free media (SFM), based on good manufacture practices (GMP), have recently been used and seem to be a viable option. The aim of this study was to evaluate the results of the differentiation, maturation, and function of DCs from Acute Myeloid Leukemia patients (AML), generated in SFM and medium supplemented with autologous serum (AS). DCs were analyzed by phenotype characteristics, viability, and functionality. The results showed the possibility of generating viable DCs in all the conditions tested. In patients, the X-VIVO 15 medium was more efficient than the other media tested in the generation of DCs producing IL-12p70 (p=0.05). Moreover, the presence of AS led to a significant increase of IL-10 by DCs as compared with CellGro (p=0.05) and X-Vivo15 (p=0.05) media, both in patients and donors. We concluded that SFM was efficient in the production of DCs for immunotherapy in AML patients. However, the use of AS appears to interfere with the functional capacity of the generated DCs.