Emerging pathways in colorectal-cancer development

The past decade has seen the emergence of new pathways in the development of colorectal cancer. There is now clear evidence that subsets of these tumours do not show chromosomal instability and do not follow the suppressor pathway. Instead, about 15% of colorectal cancers are characterised by microsatellite instability (MSI). This feature arises through defective DNA mismatch repair, which is related either to a germline mutation (as in hereditary non-polyposis colorectal carcinoma) or to failure to express a mismatch-repair gene. CpG-island methylation has been linked to sporadic cancers with a high frequency of MSI. This type of methylation leads to loss of gene expression when it occurs in the promoter region of a gene. Tumours may have high or low type C (cancer-related) CpG-island methylation. When methylation affects hMLH1 (mismatch repair gene), the resultant cancer has high MSI.

Emerging concepts in colorectal neoplasia

An understanding of the mechanisms that explain the initiation and early evolution of colorectal cancer should facilitate the development of new approaches to effective prevention and intervention. This review highlights deficiencies in the current model for colorectal neoplasia in which APC mutation is placed at the point of initiation. Other genes implicated in the regulation of apoptosis and DNA repair may underlie the early development of colorectal cancer. Inactivation of these genes may occur not by mutation or loss but through silencing mediated by methylation of the gene's promoter region. hMLH1 and MGMT are examples of DNA repair genes that are silenced by methylation. Loss of expression of hMLH1 and MGMT protein has been demonstrated immunohistochemically in serrated polyps. Multiple lines of evidence point to a serrated pathway of neoplasia that is driven by inhibition of apoptosis and the subsequent inactivation of DNA repair genes by promoter methylation. The earliest lesions in this pathway are aberrant crypt foci (ACF). These may develop Into hyperplastic polyps or transform while still of microscopic size into admixed polyps, serrated adenomas, or traditional adenomas. Cancers developing from these lesions may show high- or low-level microsatellite instability (MSI-H and MSI-L, respectively) or may be microsatellite stable (MSS). The suggested clinical model for this alternative pathway is the condition hyperplastic polyposis. If colorectal cancer is a heterogeneous disease comprising discrete subsets that evolve through different pathways, it is evident that these subsets will need to be studied individually in the future.

Global distribution and genetic discontinuities of mangroves - emerging patterns in the evolution of Rhizophora

Mangroves are often described as a group of plants with common features and common origins based mostly on their broad distributional patterns, together with an erroneous view of comparable abilities in long-distance dispersal. However, whilst mangroves have common needs to adapt to rigorous environmental constraints associated with regular seawater inundation, individual taxa have developed different strategies and characteristics. Since mangroves are a genetically diverse group of mostly flowering plants, they may also have evolved at quite different geological periods, dispersed at different rates from different locations and developed different adaptive strategies. Current distributions of individual taxa show numerous instances of unusual extant distribution which demonstrate finite dispersal limitations, especially across open water. Our preliminary assessment of broad distribution and discontinuities reveals important patterns. Discontinuities, in the absence of current dispersal barriers, may be explained by persistent past barriers. As we learn more about discontinuities, we are beginning to appreciate their immense implications and what they might tell us about past geological conditions and how these might have influenced the distribution and evolution of mangroves. In this article, we describe emerging patterns in genetic relationships and distributions based on both current knowledge and preliminary results of our studies of molecular and morphometric characteristics of Rhizophora species in the Indo West Pacific region.

Managing strategic challenges in community sector organisations

Like those in other sectors, managers in community-based organisations face an uncertain and challenging future. Research and writing about the community sector (non-government, notjor-profit, or third seclOr) has canvassed a wide range of issues. A selective review of the recent literature reveals the breadth of research interest in the challenges facing community sector managers. While some reflection on the implications for managers of current economic and social policy contexts is crucial for this sector, research effort needs to be focused on understanding how third sector managers construe their current strategic challenges and the strategies they use to address them A small sample ofmanagers working in a regional area in South East Queensland was asked to identify current strategic concerns related to the future viability of their organisations. The key issues raised by managers are compared with the issues raised in the research literature. Results -to date indicate that managers' concerns are reflected in the research literature, but that managers are also concemed about the current trends in social policy towards collaboration, amalgamation, and pannership. Implications of these findings for managers operating in this sector are discussed.

Chinese energy policy progress and challenges in the transition to low carbon development, 2006-2013

If the world is not to jeopardize the chances for human life on Earth, climate change must be mitigated; therefore, achieving low carbon development is crucial. China is the world's greatest GHG emitter, energy producer and energy consumer; investigating its energy-climate policy developments and international positions are of utmost importance to understand and tackle current stumbling blocks of the global energy and climate governance.

New challenges in mathematics for the european higher education

In this paper we will talk about a math project submitted to the Lifelong Learning Programme. European higher education needs a reform in order to play its full role in the Europe of Knowledge. Modernisation of higher education is necessary in the areas of curricula (Bologna process), funding and governance so that higher education institutions can face the challenges posed by globalisation and contribute more effectively to the training and retraining of the European workforce. On the other hand Mathematics is an essential component of all educational systems. Mathematical literacy is being scrutinized in assessment efforts such as the OCDE Programme for International Student Assessment (PISA). This showed a low level in Europe. Due to the Bologna Process, which brought several didactical implications for Higher Education (HE) institutions, there is the need of lifelong learning. This evolution is in conflict with the earlier mentioned lack of competencies on basic sciences, such as Mathematics. Forced by this duality, efforts are combined to share expertise in the Math field and the integration of pedagogical methodologies becomes a necessity. Thus, several European countries have proposed an International Project to the Lifelong Learning Programme, Action ERASMUS Modernisation of Higher Education, to make institutions more attractive and more responsive to the needs of the labour market, citizens and society at large. One of the main goals of the project is to attract students to math through high-quality instructional units in an understandable, exciting and attractive way.

Advances and challenges in oral health after a decade of the “Smiling Brazil” Program

ABSTRACT OBJECTIVE To analyze oral health work changes in primary health care after Brazil’s National Oral Health Policy Guidelines were released. METHODS A literature review was conducted on Medline, LILACS, Embase, SciELO, Biblioteca Virtual em Saúde, and The Cochrane Library databases, from 2000 to 2013, on elements to analyze work changes. The descriptors used included: primary health care, family health care, work, health care policy, oral health care services, dentistry, oral health, and Brazil. Thirty-two studies were selected and analyzed, with a predominance of qualitative studies from the Northeast region with workers, especially dentists, focusing on completeness and quality of care. RESULTS Observed advances focused on educational and permanent education actions; on welcoming, bonding, and accountability. The main challenges were related to completeness; extension and improvement of care; integrated teamwork; working conditions; planning, monitoring, and evaluation of actions; stimulating people’s participation and social control; and intersectorial actions. CONCLUSIONS Despite the new regulatory environment, there are very few changes in oral health work. Professionals tend to reproduce the dominant biomedical model. Continuing efforts will be required in work management, training, and permanent education fields. Among the possibilities are the increased engagement of managers and professionals in a process to understand work dynamics and training in the perspective of building significant changes for local realities.

Challenges in the creation and development of a mathematics MOOC

The fast development of distance learning tools such as Open Educational Resources (OER) and Massive Open Online Courses (MOOC or MOOCs) are indicators of a shift in the way in which digital teaching and learning are understood. MOOC are a new style of online classes that allow any person with web access, anywhere, usually free of charge, to participate through video lectures, computer graded tests and discussion forums. They have been capturing the attention of many higher education institutions around the world. This paper will give us an overview of the “Introduction to Differential Calculus” a MOOC Project, created by an engaged volunteer team of Mathematics lecturers from four schools of the Polytechnic Institute of Oporto (IPP). The MOOC theories and their popularity are presented and complemented by a discussion of some MOOC definitions and their inherent advantages and disadvantages. It will also explore what MOOC mean for Mathematics education. The Project development is revealed by focusing on used MOOC structure, as well as the quite a lot of types of course materials produced. It ends with a presentation of a short discussion about problems and challenges met throughout the development of the project. It is also our goal to contribute for a change in the way teaching and learning Mathematics is seen and practiced nowadays, trying to make education more accessible to as many people as possible and increase our institution (IPP) recognition.

CHAGASIC MENINGOENCEPHALITIS IN AN HIV INFECTED PATIENT WITH MODERATE IMMUNOSUPPRESSION: PROLONGED SURVIVAL AND CHALLENGES IN THE HAART ERA

The reactivation of Chagas disease in HIV infected patients presents high mortality and morbidity. We present the case of a female patient with confirmed Chagasic meningoencephalitis as AIDS-defining illness. Interestingly, her TCD4+ lymphocyte cell count was 318 cells/mm3. After two months of induction therapy, one year of maintenance with benznidazol, and early introduction of highly active antiretroviral therapy (HAART), the patient had good clinical, parasitological and radiological evolution. We used a qualitative polymerase chain reaction for the monitoring of T. cruzi parasitemia during and after the treatment. We emphasize the potential value of molecular techniques along with clinical and radiological parameters in the follow-up of patients with Chagas disease and HIV infection. Early introduction of HAART, prolonged induction and maintenance of antiparasitic therapy, and its discontinuation are feasible, in the current management of reactivation of Chagas disease.

PARACOCCIDIOIDOMYCOSIS: CHALLENGES IN THE DEVELOPMENT OF A VACCINE AGAINST AN ENDEMIC MYCOSIS IN THE AMERICAS

SUMMARYParacoccidioidomycosis (PCM), caused by Paracoccidioides spp, is an important endemic mycosis in Latin America. There are two recognized Paracoccidioides species, P. brasiliensis and P. lutzii, based on phylogenetic differences; however, the pathogenesis and disease manifestations of both are indistinguishable at present. Approximately 1,853 (~51,2%) of 3,583 confirmed deaths in Brazil due to systemic mycoses from 1996-2006 were caused by PCM. Antifungal treatment is required for patients with PCM. The initial treatment lasts from two to six months and sulfa derivatives, amphotericin B, azoles and terbinafine are used in clinical practice; however, despite prolonged therapy, relapses are still a problem. An effective Th1-biased cellular immune response is essential to control the disease, which can be induced by exogenous antigens or modulated by prophylactic or therapeutic vaccines. Stimulation of B cells or passive transference of monoclonal antibodies are also important means that may be used to improve the efficacy of paracoccidioidomycosis treatment in the future. This review critically details major challenges facing the development of a vaccine to combat PCM.