Design considerations for large space electric power systems

As power levels of spacecraft rise to the 50 to 100 kW range, it becomes apparent that low voltage (28 V) dc power distribution and management systems will not operate efficiently at these higher power levels. The concept of transforming a solar array voltage at 150 V dc into a 1000 V ac distribution system operating at 20 kHz is examined. The transformation is accomplished with series-resonant inverter by using a rotary transformer to isolate the solar array from the spacecraft. The power can then be distributed in any desired method such as three phase delta to delta. The distribution voltage can be easily transformed to any desired load voltage and operating frequency. The reasons for the voltage limitations on the solar array due to plasma interactions and the many advantages of a high voltage, high frequency at distribution system are discussed

Os bancos brasileiros na economia: 1906-1918

This article analyses the balance sheets of six important Brazilian banks during the period 1906 1918. By studying the volume and nature of credit extended, the conclusion is reached that these banks reacted to economic cycles in economically rational manners. They adjusted their lending activities in ways which responded to supply and demand, and to profit and risk concerns.Este artigo analisa os balancetes de seis importantes bancos brasileiros durante o período 1906-1918. Por meio da análise do volume e do tipo de crédito conclui-se que tais bancos reagiram aos ciclos econômicos de formas economicamente racionais. Os referidos bancos adaptaram suas políticas de empréstimos de modo a que estas respondessem as condições de oferta e procura, bem como aos interesses de lucro e risco

Here one year, gone the next? Investigating persistence of frequent emergency department attendance: a retrospective study in Australia

Objectives Patients are presenting to emergency departments (EDs) with increasing complexity at rates beyond population growth and ageing. Intervention studies target patients with 12 months or less of frequent attendance. However, these interventions are not well targeted since most patients do not remain frequent attenders. This paper quantifies temporary and ongoing frequent attendance and contrasts risk factors for each group. Design Retrospective population-based study using 10 years of longitudinal data. Setting An Australian geographic region that includes metropolitan and rural EDs. Participants 332 100 residents visited any ED during the study period. Main outcome measure Frequent attendance was defined as seven or more visits to any ED in the region within a 12-month period. Temporary frequent attendance was defined as meeting this threshold only once, and ongoing more than once. Risk factors for temporary and ongoing frequent attenders were identified using logistic regression models for adults and children. Results Of 8577 frequent attenders, 80.1% were temporary and 19.9% ongoing (12.9% repeat, 7.1% persistent). Among adults, ongoing were more likely than temporary frequent attenders to be young to middle aged (aged 25-64 years), and less likely to be from a high socioeconomic area or be admitted. Ongoing frequent attenders had higher rates of non-injury presentations, in particular substance-related (OR=2.5, 99% CI 1.1 to 5.6) and psychiatric illness (OR=2.9, 99% CI 1.8 to 4.6). In comparison, children who were ongoing were more likely than temporary frequent attenders to be aged 5-15 years, and were not more likely to be admitted (OR=2.7, 99% CI 0.7 to 10.9). Conclusions Future intervention studies should distinguish between temporary and ongoing frequent attenders, develop specific interventions for each group and include rigorous evaluation

Chemical informatics uncovers a new role for moexipril as a novel inhibitor of cAMP phosphodiesterase-4 (PDE4)

PDE4 is one of eleven known cyclic nucleotide phosphodiesterase families and plays a pivotal role in mediating hydrolytic degradation of the important cyclic nucleotide second messenger, cyclic 3′5′ adenosine monophosphate (cAMP). PDE4 inhibitors are known to have anti-inflammatory properties, but their use in the clinic has been hampered by mechanism-associated side effects that limit maximally tolerated doses. In an attempt to initiate the development of better-tolerated PDE4 inhibitors we have surveyed existing approved drugs for PDE4-inhibitory activity. With this objective, we utilised a high-throughput computational approach that identified moexipril, a well tolerated and safe angiotensin-converting enzyme (ACE) inhibitor, as a PDE4 inhibitor. Experimentally we showed that moexipril and two structurally related analogues acted in the micro molar range to inhibit PDE4 activity. Employing a FRET-based biosensor constructed from the nucleotide binding domain of the type 1 exchange protein activated by cAMP, EPAC1, we demonstrated that moexipril markedly potentiated the ability of forskolin to increase intracellular cAMP levels. Finally, we demonstrated that the PDE4 inhibitory effect of moexipril is functionally able to induce phosphorylation of the Hsp20 by cAMP dependent protein kinase A. Our data suggest that moexipril is a bona fide PDE4 inhibitor that may provide the starting point for development of novel PDE4 inhibitors with an improved therapeutic window

Clinical research without consent in adults in the emergency setting: a review of patient and public views

<p>Abstract</p> <p>Background</p> <p>In emergency research, obtaining informed consent can be problematic. Research to develop and improve treatments for patients admitted to hospital with life-threatening and debilitating conditions is much needed yet the issue of research without consent (RWC) raises concerns about unethical practices and the loss of individual autonomy. Consistent with the policy and practice turn towards greater patient and public involvement in health care decisions, in the US, Canada and EU, guidelines and legislation implemented to protect patients and facilitate acute research with adults who are unable to give consent have been developed with little involvement of the lay public. This paper reviews research examining public opinion regarding RWC for research in emergency situations, and whether the rules and regulations permitting research of this kind are in accordance with the views of those who ultimately may be the most affected.</p> <p>Methods</p> <p>Seven electronic databases were searched: Medline, Embase, CINAHL, Cochrane Database of Systematic Reviews, Philosopher's Index, Age Info, PsychInfo, Sociological Abstracts and Web of Science. Only those articles pertaining to the views of the public in the US, Canada and EU member states were included. Opinion pieces and those not published in English were excluded.</p> <p>Results</p> <p>Considering the wealth of literature on the perspectives of professionals, there was relatively little information about public attitudes. Twelve studies employing a range of research methods were identified. In five of the six questionnaire surveys around half the sample did <it>not </it>agree generally with RWC, though paradoxically, a higher percentage would <it>personally </it>take part in such a study. Unfortunately most of the studies were not designed to investigate individuals' views in any depth. There also appears to be a level of mistrust of medical research and some patients were more likely to accept an experimental treatment 'outside' of a research protocol.</p> <p>Conclusion</p> <p>There are too few data to evaluate whether the rules and regulations permitting RWC protects – or is acceptable to – the public. However, any attempts to engage the public should take place in the context of findings from further basic research to attend to the apparently paradoxical findings of some of the current surveys.</p

Iron Uptake via DMT1 Integrates Cell Cycle with JAK-STAT3 Signaling to Promote Colorectal Tumorigenesis

Dietary iron intake and systemic iron balance are implicated in colorectal cancer (CRC) development, but the means by which iron contributes to CRC are unclear. Gene expression and functional studies demonstrated that the cellular iron importer, divalent metal transporter 1 (DMT1), is highly expressed in CRC through hypoxia-inducible factor 2alpha-dependent transcription. Colon-specific Dmt1 disruption resulted in a tumor-selective inhibitory effect of proliferation in mouse colon tumor models. Proteomic and genomic analyses identified an iron-regulated signaling axis mediated by cyclin-dependent kinase 1 (CDK1), JAK1, and STAT3 in CRC progression. A pharmacological inhibitor of DMT1 antagonized the ability of iron to promote tumor growth in a CRC mouse model and a patient-derived CRC enteroid orthotopic model. Our studies implicate a growth-promoting signaling network instigated by elevated intracellular iron levels in tumorigenesis, offering molecular insights into how a key dietary component may contribute to CRC

Key stakeholder perceptions about consent to participate in acute illness research: a rapid, systematic review to inform epi/pandemic research preparedness

Background A rigorous research response is required to inform clinical and public health decision-making during an epi/pandemic. However, the ethical conduct of such research, which often involves critically ill patients, may be complicated by the diminished capacity to consent and an imperative to initiate trial therapies within short time frames. Alternative approaches to taking prospective informed consent may therefore be used. We aimed to rapidly review evidence on key stakeholder (patients, their proxy decision-makers, clinicians and regulators) views concerning the acceptability of various approaches for obtaining consent relevant to pandemic-related acute illness research. Methods We conducted a rapid evidence review, using the Internet, database and hand-searching for English language empirical publications from 1996 to 2014 on stakeholder opinions of consent models (prospective informed, third-party, deferred, or waived) used in acute illness research. We excluded research on consent to treatment, screening, or other such procedures, non-emergency research and secondary studies. Papers were categorised, and data summarised using narrative synthesis. Results We screened 689 citations, reviewed 104 full-text articles and included 52. Just one paper related specifically to pandemic research. In other emergency research contexts potential research participants, clinicians and research staff found third-party, deferred, and waived consent to be acceptable as a means to feasibly conduct such research. Acceptability to potential participants was motivated by altruism, trust in the medical community, and perceived value in medical research and decreased as the perceived risks associated with participation increased. Discrepancies were observed in the acceptability of the concept and application or experience of alternative consent models. Patients accepted clinicians acting as proxy-decision makers, with preference for two decision makers as invasiveness of interventions increased. Research regulators were more cautious when approving studies conducted with alternative consent models; however, their views were generally under-represented. Conclusions Third-party, deferred, and waived consent models are broadly acceptable to potential participants, clinicians and/or researchers for emergency research. Further consultation with key stakeholders, particularly with regulators, and studies focused specifically on epi/pandemic research, are required. We highlight gaps and recommendations to inform set-up and protocol development for pandemic research and institutional review board processes

Banco Britânico no Brasil durante a Primeira República

This paper delves into the workings of British banks in Brazil in order to assess how they affected the development of the domestic Brazilian banking system during the First Republic (1889-1930.) The paper is concerned with the role of British banks within the domestic economy, in contrast to the role of the banks in the global trading network. It assesses five avenues of influence by which British commercial banks had a role in the Brazilian banking system in ways that differed from domestically owned and managed counterpart: providing a model for a “national” banking system, serving as a business model for domestic banks, offering foreign exchange services beyond the constraints imposed on domestic banks, injecting new capital and reserves in periods of crisis, and supporting the expansion of business transactions within Brazil. The paper also documents the decline of British presence during the period and considers the reasons for the decline.Este artículo investiga el funcionamiento de los bancos británicos en Brasil, con el fin de evaluar cómo afectaron el desarrollo del sistema bancario interno brasileño durante la Primeira República (1889-1930). El artículo se centra en el papel de los bancos británicos dentro de la economía nacional, en contraste con el papel de los bancos en la red comercial munidal. Evalúa cinco ejes de influencia mediante los cuales los bancos comerciales británicos desempeñaron un papel en el sistema bancario brasileño en formas que diferían de la propiedad de contraparte doméstica y administrada: proporcionando un modelo para un sistema bancario "nacional", que sirvió como modelo de negocios para los bancos nacionales, ofreciendo servicios de cambio de divisas, además de las restricciones impuestas a los bancos nacionales, inyectar nuevo capital y reservas en tiempos de crisis, y apoyar la expansión de las operaciones comerciales en Brasil. El artículo también documenta el declive de la presencia británica en el período y considera las razones del declive.Este artigo investiga o funcionamento de bancos britânicos no Brasil, a fim de avaliar a forma como elas afetaram o desenvolvimento do sistema bancário doméstico brasileiro durante a Primeira República (1889-1930). O artigo está voltado para o papel dos bancos britânicos dentro da economia doméstica, em contraste com o papel dos bancos na rede de comércio global. Ele avalia cinco eixos de influência pelo qual os bancos comerciais britânicos tiveram um papel no sistema bancário brasileiro de maneira que diferiam da propriedade interna e gerida contraparte: o fornecimento de um modelo para um sistema bancário “nacional”, servindo como um modelo de negócio para os bancos nacionais, oferecendo serviços de câmbio, além das restrições impostas aos bancos domésticos, injetar novo capital e reservas em períodos de crise, e apoiar a expansão das operações de negócios no Brasil. O artigo também documenta o declínio da presença britânica no período e considera as razões para o declínio