Present and future pharacotherapy for heart failure

The pharmacotherapy currently recommended by the American College of Cardiology and the American Heart Association for heart failure (HF) is a diuretic, an angiotensin-converting enzyme inhibitor (ACEI), a β-adrenoceptor antagonist and (usually) digitalis. This current treatment of HF may be improved by optimising the dose of ACEI used, as increasing the dose of lisinopril increases its benefits in HF. Selective angiotensin receptor-1 (AT1) antagonists are effective alternatives for those who cannot tolerate ACEIs. AT1 antagonists may also be used in combination with ACEIs, as some studies have shown cumulative benefits for the combination. In addition to being used in Stage IV HF patients, in whom it has a marked benefit, spironolactone should be studied in less severe HF and in the presence of β-blockers. The use of carvedilol, extended-release metoprolol and bisoprolol should be extended to severe HF patients as these agents have been shown to decrease mortality in this group. The ancillary properties of carvedilol, particularly antagonism at prejunctional β-adrenoceptors, may give it additional benefits to selective β1-adrenoceptor antagonists. Celiprolol and bucindolol are not the β-blockers of choice in HF, as they do not decrease mortality. Although digitalis does not reduce mortality, it remains the only option for a long-term positive inotropic effect, as the long-term use of the phosphodiesterase inhibitors is associated with increased mortality. The calcium sensitising drug levosimendan may be useful in the hospital treatment of decompensated HF to increase cardiac output and improve dyspnoea and fatigue. The antiarrhythmic drug amiodarone should probably be used in patients at high risk of arrhythmic or sudden death, although this treatment may soon be superseded by the more expensive implanted cardioverter defibrillators, which are probably more effective and have fewer side effects. The natriuretic peptide nesiritide has recently been introduced for the hospital treatment of decompensated HF. Novel drugs that may be beneficial in the treatment of HF include the vasopeptidase inhibitors and the selective endothelin-A receptor antagonists but these require much more investigation. However, disappointing results have been obtained in a large clinical trial of the tumour necrosis factor α antagonist etanercept, where no likelihood of a difference between placebo and etanercept was observed. Small clinical trials with recombinant growth hormone to thicken ventricles in dilated cardiomyopathy have given variable results.

Insect chemistry and chirality

Examination of the chemistry of a number of Australian insect species provided examples of unusual structures and encouraged determinations of their absolute stereochemistry by stereocontrolled syntheses and chromatographic comparisons. Inter alia, studies with the fruit-spotting bug (Amblypelta nitida), certain parasitic wasps (Biosteres sp.), the aposematic shield bug (Cantao parentum), and various species of scarab grubs are summarized. The determination of enantiomeric excesses (ee's) for component epoxides, lactones, spiroacetals, and allenes are described. Stereochemical and related aspects of the biosynthesis of spiroacetals in certain fruit-fly species (Bactrocerae sp.) are also presented.

Cytotoxic iron chelators: Characterization of the structure, solution chemistry and redox activity of ligands and iron complexes of the di-2-pyridyl ketone isonicotinoyl hydrazone (HPKIH) analogues

Di-2-pyridyl ketone isonicotinoyl hydrazone (HPKIH) and a range of its analogues comprise a series of monobasic acids that are capable of binding iron (Fe) as tridentate (N,N,O) ligands. Recently, we have shown that these chelators are highly cytotoxic, but show selective activity against cancer cells. Particularly interesting was the fact that cytotoxicity of the HPKIH analogues is maintained even after complexation with Fe. To understand the potent anti-tumor activity of these compounds, we have fully characterized their chemical properties. This included examination of the solution chemistry and X-ray crystal structures of both the ligands and Fe complexes from this class and the ability of these complexes to mediate redox reactions. Potentiometric titrations demonstrated that all chelators are present predominantly in their charge-neutral form at physiological pH (7.4), allowing access across biological membranes. Keto-enol tautomerism of the ligands was identified, with the tautomers exhibiting distinctly different protonation constants. Interestingly, the chelators form low-spin (diamagnetic) divalent Fe complexes in solution. The chelators form distorted octahedral complexes with Fe-II, with two tridentate ligands arranged in a meridional fashion. Electrochemistry of the Fe complexes in both aqueous and non-aqueous solutions revealed that the complexes are oxidized to their ferric form at relatively high potentials, but this oxidation is coupled to a rapid reaction with water to form a hydrated (carbinolamine) derivative, leading to irreversible electrochemistry. The Fe complexes of the HPKIH analogues caused marked DNA degradation in the presence of hydrogen peroxide. This observation confirms that Fe complexes from the HPKIH series mediate Fenton chemistry and do not repel DNA. Collectively, studies on the solution chemistry and structure of these HPKIH analogues indicate that they can bind cellular Fe and enhance its redox activity, resulting in oxidative damage to vital biomolecules.

Kidney targeting and puncturing during percutaneous nephrolithotomy: recent advances and future perspectives

Background and Purpose: Precise needle puncture of the kidney is a challenging and essential step for successful percutaneous nephrolithotomy (PCNL). Many devices and surgical techniques have been developed to easily achieve suitable renal access. This article presents a critical review to address the methodologies and techniques for conducting kidney targeting and the puncture step during PCNL. Based on this study, research paths are also provided for PCNL procedure improvement. Methods: Most relevant works concerning PCNL puncture were identified by a search of Medline/PubMed, ISI Web of Science, and Scopus databases from 2007 to December 2012. Two authors independently reviewed the studies. Results: A total of 911 abstracts and 346 full-text articles were assessed and discussed; 52 were included in this review as a summary of the main contributions to kidney targeting and puncturing. Conclusions: Multiple paths and technologic advances have been proposed in the field of urology and minimally invasive surgery to improve PCNL puncture. The most relevant contributions, however, have been provided by the applicationofmedical imaging guidance, newsurgical tools,motion tracking systems, robotics, andimage processing and computer graphics. Despite the multiple research paths for PCNL puncture guidance, no widely acceptable solution has yet been reached, and it remains an active and challenging research field. Future developments should focus on real-time methods, robust and accurate algorithms, and radiation free imaging techniques

Kidney targeting and puncturing during percutaneous nephrolithotomy:recent advances and future perspectives

Precise needle puncture of the kidney is a challenging and essential step for successful percutaneous nephrolithotomy (PCNL). Many devices and surgical techniques have been developed to easily achieve suitable renal access. This article presents a critical review to address the methodologies and techniques for conducting kidney targeting and the puncture step during PCNL. Based on this study, research paths are also provided for PCNL procedure improvement. Methods: Most relevant works concerning PCNL puncture were identified by a search of Medline/PubMed, ISI Web of Science, and Scopus databases from 2007 to December 2012. Two authors independently reviewed the studies.

Data mining applications in power systems - case-studies and future trends

Presently power system operation produces huge volumes of data that is still treated in a very limited way. Knowledge discovery and machine learning can make use of these data resulting in relevant knowledge with very positive impact. In the context of competitive electricity markets these data is of even higher value making clear the trend to make data mining techniques application in power systems more relevant. This paper presents two cases based on real data, showing the importance of the use of data mining for supporting demand response and for supporting player strategic behavior.

Quality-of-service in wireless sensor networks: state-of-the-art and future directions

Wireless sensor networks (WSNs) are one of today’s most prominent instantiations of the ubiquituous computing paradigm. In order to achieve high levels of integration, WSNs need to be conceived considering requirements beyond the mere system’s functionality. While Quality-of-Service (QoS) is traditionally associated with bit/data rate, network throughput, message delay and bit/packet error rate, we believe that this concept is too strict, in the sense that these properties alone do not reflect the overall quality-ofservice provided to the user/application. Other non-functional properties such as scalability, security or energy sustainability must also be considered in the system design. This paper identifies the most important non-functional properties that affect the overall quality of the service provided to the users, outlining their relevance, state-of-the-art and future research directions.

Change Processes and Future Perspectives in the Knowledge Society. The Example of Clothing and Textile Industry

The paper examines change processes und future perspectives in the knowledge society. It presents the clothing and textile industry as an example for a transforming industry in a global economy. The paper reviews existing future studies, which have surveyed change processes and future developments in the clothing and textile industry. Main goals of the review are the identification of changes in work and the description of the restructuring of global value chains within the clothing and textile sector. The paper also highlights major current trends, drivers of change and future prospects in this sector.

GIS from a cultural heritage perspective: when past and future collide

Dissertação apresentada como requisito parcial para obtenção do grau de Mestre em Ciência e Sistemas de Informação Geográfica

Are societal changes new? Questions or trends and future perceptions on knowledge-based economy

With the emergence of a global division of labour, the internationalisation of markets and cultures, the growing power of supranational organisations and the spread of new information technologies to every field of life, it starts to appear a different kind of society, different from the industrial society, and called by many as ‘the knowledge-based economy’, emphasizing the importance of information and knowledge in many areas of work and organisation of societies. Despite the common trends of evolution, these transformations do not necessarily produce a convergence of national and regional social and economic structures, but a diversity of realities emerging from the relations between economic and political context on one hand and the companies and their strategies on the other. In this sense, which future can we expect to the knowledge economy? How can we measure it and why is it important? This paper will present some results from the European project WORKS – Work organisation and restructuring in the knowledge society (6th Framework Programme), focusing the future visions and possible future trends in different countries, sectors and industries, given empirical evidences of the case studies applied in several European countries, underling the importance of foresight exercises to design policies, prevent uncontrolled risks and anticipate alternatives, leading to different ‘knowledge economies’ and not to the ‘knowled

Bridging present and future of brain-computer interfaces: an assessment of impacts

Based on the report for the “Project III” unit of the PhD programme on Technology Assessment under the supervision of Prof. António B. Moniz. This report was discussed also at the 2nd Winter School on Technology Assessment held at Universidade Nova de Lisboa, Caparica Campus, Portugal on December 2011.

The compliance function in banking: Perspective and future in the age of globalization

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Management from the NOVA – School of Business and Economics