In vitro prevention of the emergence of daptomycin resistance in Staphylococcus aureus and enterococci following combination with amoxicillin/clavulanic acid or ampicillin.

Daptomycin is bactericidal against meticillin-resistant Staphylococcus aureus (MRSA), glycopeptide-intermediate-resistant S. aureus (GISA) and vancomycin-susceptible and -resistant enterococci. However, selection for daptomycin-resistant derivatives has occasionally been reported during therapy in humans. Here we evaluate whether selection for daptomycin-resistant S. aureus or enterococci could be prevented in vitro by combining daptomycin with amoxicillin/clavulanic acid, ampicillin, gentamicin or rifampicin. Six strains of S. aureus (four MRSA and two GISA) and four strains of enterococci (two Enterococcus faecalis and two Enterococcus faecium) were serially exposed in broth to two-fold stepwise increasing concentrations of daptomycin alone or in combination with a fixed concentration [0.25x minimum inhibitory concentration (MIC)] of either of the second agents. The daptomycin MIC was examined after each cycle. Exposure to daptomycin alone gradually selected for S. aureus and enterococci with an increased MIC. Gentamicin did not prevent the emergence of daptomycin-resistant bacteria. Rifampicin was also unable to prevent daptomycin resistance, although resistance was slightly delayed. In contrast, amoxicillin/clavulanic acid or ampicillin prevented or greatly delayed the selection of daptomycin-resistant mutants in S. aureus and enterococci, respectively. Addition of amoxicillin/clavulanic acid or ampicillin to daptomycin prevents, or greatly delays, daptomycin resistance in vitro. Future studies in animal models are needed to predict the utility of these combinations in humans.

Testing the descriptive performance of the rank-dependent utility in the domain of health profiles

Expected utility theory (EUT) has been challenged as a descriptive theoryin many contexts. The medical decision analysis context is not an exception.Several researchers have suggested that rank dependent utility theory (RDUT)may accurately describe how people evaluate alternative medical treatments.Recent research in this domain has addressed a relevant feature of RDU models-probability weighting-but to date no direct test of this theoryhas been made. This paper provides a test of the main axiomatic differencebetween EUT and RDUT when health profiles are used as outcomes of riskytreatments. Overall, EU best described the data. However, evidence on theediting and cancellation operation hypothesized in Prospect Theory andCumulative Prospect Theory was apparent in our study. we found that RDUoutperformed EU in the presentation of the risky treatment pairs in whichthe common outcome was not obvious. The influence of framing effects onthe performance of RDU and their importance as a topic for future researchis discussed.

The benefits of limited feedback in organizations

In most firms, managers periodically assess workers' performance. Evidence suggeststhat managers withhold information during these reviews, and some observersargue that this necessarily reduces surplus. This paper assesses the validity of thisargument when workers have career concerns. Disclosure has two effects: it exposesthe worker to uncertainty about future effort levels, but allows him to use current effortto influence his employer's beliefs about future effort. The surplus-maximizingdisclosure policy reveals output realizations in the center of the distribution, butnot in the tails. Thus, it is efficient for firms to reveal some but not all performanceinformation.

English as a world language: its role as a lingua francaa sociolinguistic profile of students of secondary schools in Santiago Island, in the Archipelago of Cape Verde

Esta tese centra-se em aspectos relevantes do inglês como uma língua universal, no actual contexto globalizado e examina possíveis mudanças relacionadas com o seu uso, em especial no continente africano, particularmente no caso de Cabo Verde, no sentido de ponderar eventuais alternativas nas pedagogias linguísticas no ensino desta língua que impliquem uma adaptação à realidade contemporânea. Uma vez que, nos nossos tempos, o inglês é a língua de eleição para a comunicação intercultural entre povos com várias experiências culturais e linguísticas, o conhecimento deste idioma torna-se, a cada dia que passa, impreterível e indispensável, na interacção intercultural. Em África, as funções desempenhadas pelo inglês são complexas; além da língua inglesa ser usada para comunicação entre etnias, com o estatuto de língua franca, também tem o papel de preservar a identidade nacional e de estabelecer a unidade entre os povos da mesma nação. Por conseguinte, é de considerar talvez ainda com mais pertinência, a adopção de uma nova filosofia de pedagogia de ensino que permita dotar os seus cidadãos de capacidades que lhes possibilitem comunicar de forma inteligível com povos de outras culturas e línguas. O primeiro capítulo aborda aspectos teóricos relacionados com a expansão, comunicação e mudança associadas à língua inglesa e suas implicações no ensino em países onde esta não é língua nativa (L1). O segundo capítulo reflecte, em primeiro lugar, sobre a situação linguística em África e as línguas francas predominantes no continente, incluindo a língua inglesa. Considera também questões relacionadas com o multilinguismo e a identidade, bem como assuntos relacionados com as implicações da diversidade linguística para a educação dos povos africanos.

The three phases of the ensemble forecasting of niche models: geographic range and shifts in climatically suitable areas of Utetheisa ornatrix (Lepidoptera, Arctiidae)

Species' geographic ranges are usually considered as basic units in macroecology and biogeography, yet it is still difficult to measure them accurately for many reasons. About 20 years ago, researchers started using local data on species' occurrences to estimate broad scale ranges, thereby establishing the niche modeling approach. However, there are still many problems in model evaluation and application, and one of the solutions is to find a consensus solution among models derived from different mathematical and statistical models for niche modeling, climatic projections and variable combination, all of which are sources of uncertainty during niche modeling. In this paper, we discuss this approach of ensemble forecasting and propose that it can be divided into three phases with increasing levels of complexity. Phase I is the simple combination of maps to achieve a consensual and hopefully conservative solution. In Phase II, differences among the maps used are described by multivariate analyses, and Phase III consists of the quantitative evaluation of the relative magnitude of uncertainties from different sources and their mapping. To illustrate these developments, we analyzed the occurrence data of the tiger moth, Utetheisa ornatrix (Lepidoptera, Arctiidae), a Neotropical moth species, and modeled its geographic range in current and future climates.

Transcatheter aortic valve implantation (TAVI): state of the art techniques and future perspectives.

Transcatheter aortic valve therapies are the newest established techniques for the treatment of high risk patients affected by severe symptomatic aortic valve stenosis. The transapical approach requires a left anterolateral mini-thoracotomy, whereas the transfemoral method requires an adequate peripheral vascular access and can be performed fully percutaneously. Alternatively, the trans-subclavian access has been recently proposed as a third promising approach. Depending on the technique, the fine stent-valve positioning can be performed with or without contrast injections. The transapical echo-guided stent-valve implantation without angiography (the Lausanne technique) relies entirely on transoesophageal echocardiogramme imaging for the fine stent-valve positioning and it has been proved that this technique prevents the onset of postoperative contrast-related acute kidney failure. Recent published reports have shown good hospital outcomes and short-term results after transcatheter aortic valve implantation, but there are no proven advantages in using the transfemoral or the transapical technique. In particular, the transapical series have a higher mean logistic Euroscore of 27-35%, a procedural success rate above 95% and a mean 30-day mortality between 7.5 and 17.5%, whereas the transfemoral results show a lower logistic Euroscore of 23-25.5%, a procedural success rate above 90% and a 30-day mortality of 7-10.8%. Nevertheless, further clinical trials and long-term results are mandatory to confirm this positive trend. Future perspectives in transcatheter aortic valve therapies would be the development of intravascular devices for the ablation of the diseased valve leaflets and the launch of new stent-valves with improved haemodynamic, different sizes and smaller delivery systems.

Charting the Future of Iowa's Courts, 1996

A description of the direction that the court system in Iowa needs to follow to ensure future success.

Orchid bee baits attracting bees of the genus Megalopta (Hymenoptera, Halictidae) in Bauru region, São Paulo, Brazil: abundance, seasonality, and the importance of odors for dim-light bees

Nocturnal bees in the genus Megalopta Smith, 1853 are generally collected using artificial light sources. However, between 1993 and 2000, a total of 946 females (no males were captured) were captured using aromatic baits commonly used for orchid bees (Euglossini) in five localities in Bauru region, São Paulo, Brazil. Aromatic compounds used in bait traps were: benzyl acetate, eucalyptol, eugenol, skatole, methyl salicylate, and vanillin. The Megalopta species collected were: M. guimaraesi (71.2% of total number of specimens), M. amoena (28.1%), and M. aegis (0.6%). Using the data from these traps, we showed that there was a positive and significant correlation between the abundance of individuals and meteorological factors, rainfall and temperature. Bees were more commonly collected in the spring (September to December) and summer (December to March) than in the autumn and winter, the latter characterized for being a drier and colder period. Variations in the abundance were also detected among localities and years. The most attractive compounds were eugenol (54%), methyl salicylate (22%), and eucalyptol (16%). The ability to detect smells may have an important role in searching for flowers during dim-light conditions. We suggest the use of aromatic compounds in future studies on the biology of Megalopta in the Neotropical region.

Inflammation and TCR Signal Strength Determine the Breadth of the T Cell Response in a Bim-Dependent Manner.

Generating a diverse T cell memory population through vaccination is a promising strategy to overcome pathogen epitope variability and tolerance to tumor Ags. The effector and memory pool becomes broad in TCR diversity by recruiting high- and low-affinity T cells. We wanted to determine which factors dictate whether a memory T cell pool has a broad versus focused repertoire. We find that inflammation increases the magnitude of low- and high-affinity T cell responses equally well, arguing against a synergistic effect of TCR and inflammatory signals on T cell expansion. We dissect the differential effects of TCR signal strength and inflammation and demonstrate that they control effector T cell survival in a bim-dependent manner. Importantly, bim-dependent cell death is overcome with a high Ag dose in the context of an inflammatory environment. Our data define the framework for the generation of a broad T cell memory pool to inform future vaccine design.

Hierarchal utilization of different T-cell receptor Vbeta gene segments in the CD8(+)-T-cell response to an immunodominant Moloney leukemia virus-encoded epitope in vivo.

The CD8(+)-T-cell response to Moloney murine leukemia virus (M-MuLV)-associated antigens in C57BL/6 mice is directed against an immunodominant gag-encoded epitope (CCLCLTVFL) presented in the context of H-2D(b) and is restricted primarily to cytotoxic T lymphocytes (CTL) expressing the Valpha3.2 and Vbeta5.2 gene segments. We decided to examine the M-MuLV response in congenic C57BL/6 Vbeta(a) mice which are unable to express the dominant Valpha3.2(+) Vbeta5.2(+) T-cell receptor (TCR) due to a large deletion at the TCR locus that includes the Vbeta5.2 gene segment. Interestingly, M-MuLV-immune C57BL/6 Vbeta(a) mice were still able to reject M-MuLV-infected tumor cells and direct ex vivo analysis of peripheral blood lymphocytes from these immune mice revealed a dramatic increase in CD8(+) cells utilizing the same Valpha3.2 gene segment in association with two different Vbeta segments (Vbeta3 and Vbeta17). Surprisingly, all these CTL recognized the same immunodominant M-MuLV gag epitope. Analysis of the TCR repertoire of individual M-MuLV-immune (C57BL/6 x C57BL/6 Vbeta(a))F(1) mice revealed a clear hierarchy in Vbeta utilization, with a preferential usage of the Vbeta17 gene segment, whereas Vbeta3 and especially Vbeta5.2 were used to much lesser extents. Sequencing of TCRalpha- and -beta-chain junctional regions of CTL clones specific for the M-MuLV gag epitope revealed a diverse repertoire of TCRbeta chains in Vbeta(a) mice and a highly restricted TCRbeta-chain repertoire in Vbeta(b) mice, whereas TCRalpha-chain sequences were highly conserved in both cases. Collectively, our data indicate that the H-2D(b)-restricted M-MuLV gag epitope can be recognized in a hierarchal fashion by different Vbeta domains and that the degree of beta-chain diversity varies according to Vbeta utilization.

Change of individual BMI in Switzerland and the USA: a multilevel model for growth

Objective The aim is to analyze and compare individual BMI growth patterns of adults from Switzerland and the U.S. Methods The analyses are based on data from two population representative longitudinal household surveys, one from Switzerland, the other from the U.S. Each data set contains up to four data points for each adult individual. We use multilevel models for growth. Results It can be shown that growth patterns are different in different cohorts in the two countries: there are only small growth differences in the youngest and oldest, but large differences in the middle ages. The individual BMI increase of the middle age Swiss amounts to only half of that in the comparable U.S. individuals. Conclusion Given the much higher BMI level especially in the youngest cohort, this points to severe obesity problems in the U.S. middle aged population in the near future. A positive correlation between individual BMI level and growth may aggravate this fact.

Predicting Adverse Events in Children with Fever and Chemotherapy-Induced Neutropenia. Results of the Prospective Multicenter SPOG 2003 FN Study

PURPOSE To develop a score predicting the risk of adverse events (AEs) in pediatric patients with cancer who experience fever and neutropenia (FN) and to evaluate its performance. PATIENTS AND METHODS Pediatric patients with cancer presenting with FN induced by nonmyeloablative chemotherapy were observed in a prospective multicenter study. A score predicting the risk of future AEs (ie, serious medical complication, microbiologically defined infection, radiologically confirmed pneumonia) was developed from a multivariate mixed logistic regression model. Its cross-validated predictive performance was compared with that of published risk prediction rules. Results An AE was reported in 122 (29%) of 423 FN episodes. In 57 episodes (13%), the first AE was known only after reassessment after 8 to 24 hours of inpatient management. Predicting AE at reassessment was better than prediction at presentation with FN. A differential leukocyte count did not increase the predictive performance. The score predicting future AE in 358 episodes without known AE at reassessment used the following four variables: preceding chemotherapy more intensive than acute lymphoblastic leukemia maintenance (weight = 4), hemoglobin > or = 90 g/L (weight = 5), leukocyte count less than 0.3 G/L (weight = 3), and platelet count less than 50 G/L (weight = 3). A score (sum of weights) > or = 9 predicted future AEs. The cross-validated performance of this score exceeded the performance of published risk prediction rules. At an overall sensitivity of 92%, 35% of the episodes were classified as low risk, with a specificity of 45% and a negative predictive value of 93%. CONCLUSION This score, based on four routinely accessible characteristics, accurately identifies pediatric patients with cancer with FN at risk for AEs after reassessment.

Strategies for improving outcomes in NSCLC: a look to the future.

Advances in the management of non-small cell lung cancer (NSCLC) over the past 30 years have led to small increases in 5-year survival rates across Europe, though further improvements may require new treatment strategies. In order to improve efficiency and reduce the cost of development, future trials for new targeted agents in NSCLC should aim to recruit patients on the basis of tumour biology rather than clinical characteristics. However, identification of predictive biomarkers is required to maximise the benefits of new approaches and expedite the drug development process. Nevertheless, the NSCLC landscape is changing rapidly, and recent improvements in our understanding of the molecular biology of the disease will help in the identification of novel targeted agents as well as assisting in the development of personalised strategies for the numerous small subsets of defined NSCLC. Progress in imaging and treatment delivery is also likely to improve outcomes for patients with the disease. This article outlines recent progress in the treatment of NSCLC, identifies current challenges and describes proposals for improving the future management of the disease. It is hoped that implementation of some of these strategies will go some way to improving the outlook for patients with NSCLC.

New considerations on the management of osteoporosis in Central and Eastern Europe (CEE): summary of the "3rd Summit on Osteoporosis-CEE", November 2009, Budapest, Hungary.

INTRODUCTION: In November 2009, the "3rd Summit on Osteoporosis-Central and Eastern Europe (CEE)" was held in Budapest, Hungary. The conference aimed to tackle issues regarding osteoporosis management in CEE identified during the second CEE summit in 2008 and to agree on approaches that allow most efficient and cost-effective diagnosis and therapy of osteoporosis in CEE countries in the future. DISCUSSION: The following topics were covered: past year experience from FRAX® implementation into local diagnostic algorithms; causes of secondary osteoporosis as a FRAX® risk factor; bone turnover markers to estimate bone loss, fracture risk, or monitor therapies; role of quantitative ultrasound in osteoporosis management; compliance and economical aspects of osteoporosis; and osteoporosis and genetics. Consensus and recommendations developed on these topics are summarised in the present progress report. CONCLUSION: Lectures on up-to-date data of topical interest, the distinct regional provenances of the participants, a special focus on practical aspects, intense mutual exchange of individual experiences, strong interest in cross-border cooperations, as well as the readiness to learn from each other considerably contributed to the establishment of these recommendations. The "4th Summit on Osteoporosis-CEE" held in Prague, Czech Republic, in December 2010 will reveal whether these recommendations prove of value when implemented in the clinical routine or whether further improvements are still required.

Thérapie cellulaire régénérative en cardiologie: le futur au présent [Cell-based regenerative therapy in cardiology: the future at present].

Cell-based regenerative therapy treatment of cardiovascular diseases considered as irreversible, as acute myocardial infarction, chronic ischemic heart failure, non-ischemic dilated cardiomyopathy and refractory angina pectoris. Large randomized clinical trials with hard clinical endpoints are still necessary before considering cell-based regenerative therapy as a valuable alternative therapeutic option in cardiology.