1,480 research outputs found
Characterization of plasmids carrying CMY-2 from expanded-spectrum cephalosporin-resistant Salmonella strains isolated in the United States between 1996 and 1998
No full textSequencing of DNA from 15 expanded-spectrum cephalosporin (e.g., ceftriaxone)-resistant Salmonella isolates obtained in the United States revealed that resistance to ceftriaxone in all isolates was mediated by cmy-2. Hybridization patterns revealed three plasmid structures containing cmy-2 in these 15 isolates. These data suggest that the spread of cmy-2 among Salmonella strains is occurring through mobilization of the cmy-2 gene into different plasmid backbones and consequent horizontal transfer by conjugation
Optimizing outcomes for patients with advanced disease in chronic myelogenous leukemia
No full textThe treatment of chronic myelogenous leukemia (CML) has been revolutionized by the development of the small-molecule tyrosine kinase inhibitor imatinib. The primary target for this drug is the oncogenic BCR-ABL kinase. Five-year survival rates for patients in chronic phase CML is now greater than 80%. Patients who have advanced beyond the chronic phase to the accelerated phase or blast crisis, however, have not faired as well. Progression occurs for a variety of reasons, including late diagnosis, slow response to imatinib, and the development of imatinib-resistant clones. Imatinib resistance has, in part, been addressed with the introduction of the new BCR-ABL inhibitors, namely dasatinib and nilotinib. These drugs have shown efficacy in CML patients with wild-type BCR-ABL and some BCR-ABL mutants that are imatinib-resistant. Unfortunately, some BCR-ABL mutations remain resistant to these therapies and will require the development of alternative treatments, and other mechanisms of imatinib resistance besides BCR-ABL mutation exist. In the future, genetic and pharmacologic tests may allow the clinician to predict response to imatinib. More aggressive therapies are being considered for high-risk patients, including increased dosage of the current tyrosine kinase inhibitors, along with combination therapies. Aggressive therapy holds promise, as the data suggest that responses are improved. Unfortunately, toxicities are also increased, and thus a balance must be found to ensure safety and compliance. This is especially important for young CML patients, who hopefully will remain in remission for decades. Polymerase chain reaction analysis has become of primary importance as a means of assessing disease burden, and given the idiosyncrasies of this technique, standards must be established to allow results to be compared across different institutions. Additionally, the nature of advanced disease is being explored. Intriguingly, genetic analysis of transformed blasts from patients in blast crisis has identified numerous members of the Wnt/B-catenin pathway and JunB as being activated. Increased activity of these pathways correlates with poor response and eventual disease progression. In addition to these data, evidence is emerging associating survival of the quiescent blast cell with Wnt activity, leading to the hope that Wnt inhibitors will increase the likelihood of eradicating these cells. Other areas such as microRNA profiling and DNA methylation patterns are likely to provide important information.Francis J. Giles, Daniel J. DeAngelo, Michele Baccarani, Michael Deininger, François Guilhot, Timothy Hughes, Michael Mauro, Jerald Radich, Oliver Ottmann and Jorge Corte
Semiometrics: producing a compositional view of influence
No full textHigh-impact academic papers are not necessarily the most cited. For example, Einstein's 'Special Relativity' paper from 1905 received (and continues to receive) fewer citations from other papers than his 'Brownian Motion" paper of the same year, despite the former radically changing the course of an entire scientific discipline to a much greater extent. Similarly, 'impact' metrics using citation count alone are, it is argued, not adequate for determining the scientific influence of papers, authors or small groups of authors. Although valid, they remain controversial when used to determine influence of larger groups or journals. While the term 'impact' has become closely linked to a journal's citation-based Journal Impact Factor score, this thesis uses the term 'influence' to describe the wider effectiveness of research, combining citation and metadata analysis to allow richer calculations to be performed over large-scale document networks. As a result, more qualitative influence ratings can be determined and a broader outlook on scientific disciplines can be produced. These ratings are best applied using an ontology-based data source, allowing more efficient inference than under a traditional RDBMS system, and allowing easier integration between heterogeneous data sources. These metrics, termed 'Semantic Bibliometrics' or 'Semiometrics', can be applied at a variety of levels of granularity, allowing a compositional framework for impact and influence analysis. This thesis describes the process of data preparation, systems architecture, metric value and data integration for such a system, introducing novel approaches at all four stages, thereby creating a working semiometrics system for determining influence at different semantic levels of granularity
Chronic myelogenous leukemia in nonlymphoid blastic phase: analysis of the results of first salvage therapy with three different treatment approaches for 162 patients
No full textBACKGROUND: The prognoses of patients with chronic myelogenous leukemia in blastic phase (CML-BP) are extremely poor. Treatment of patients with nonlymphoid CML-BP is associated with very low response rates, a median survival of 2-3 months, and significant toxicities. The aim of this study was to evaluate the results of therapy in CML-BP with different treatments in relation to response rate, survival, and toxicity. METHODS: A total of 162 adults patients with a diagnosis of nonlymphoid CML-BP referred from 1986 to 1997 were included in this analysis. Only first salvage therapy was considered for the purpose of this analysis. The blastic phase of CML was defined by the presence of 30% or more blasts in the blood or bone marrow, or extramedullary disease. Ninety patients were treated with intensive chemotherapy, 31 with decitabine, and 41 with other single agents. RESULTS: Thirty-six patients (22%) had an objective response. Response rates were similar among patients treated with intensive chemotherapy (28%) or with decitabine (26%). In aggregate, other single agents showed objective response rates of 7%. The median duration of remission for all patients was 29 weeks and the median overall survival 22 weeks. Patients treated with decitabine showed a trend toward better survival, despite a higher percentage of older patients (P < 0.004). The median survival times were 29 weeks with decitabine, 21 weeks with intensive chemotherapy, and 22 weeks with other agents. When only older patients were considered, survival was significantly better with decitabine versus other treatments (P < 0.01). A multivariate analysis of prognostic factors for survival confirmed the independent, significant favorable effect of decitabine therapy (P = 0.047). In all groups complications of myelosuppression were the most significant side effects. Severe nonhematologic toxicities were not observed in patients treated with decitabine; they occurred in 20% and 17% of patients treated with intensive chemotherapy or other single agents, respectively. CONCLUSIONS: Compared with intensive chemotherapy, decitabine showed favorable results, with similar objective response rates, a better nonhematologic toxicity profile, and a trend for better survival, particularly among older patients. Studies will now attempt to combine decitabine with other promising approaches, such as homoharringtonine, low dose cytarabine, and interferon-alpha, in all CML phases
81 fJ/bit energy-to-data ratio of 850 nm vertical-cavity surface-emitting lasers for optical interconnects
No full textThis article may be downloaded for personal use only. Any other use requires prior permission of the author and AIP Publishing. This article appeared in Appl. Phys. Lett. 98, 231106 (2011) and may be found at https://doi.org/10.1063/1.3597799.Extremely energy-efficient oxide-confined high-speed 850 nm vertical-cavity surface-emitting lasers for optical interconnects are presented. Error-free performance at 17 and 25 Gb/s via a 100 m multimode fiber link is demonstrated at record high dissipation-power-efficiencies of up to 69 fJ/bit (<0.1mW/Gbps) and 99 fJ/bit, respectively. These are the most power efficient high-speed directly modulated light sources reported to date. The total energy-to-data ratio is 83 fJ/bit at 25°C and reduces to 81 fJ/bit at 55°C. These results were obtained without adjustment of driving conditions. A high -factor of 12.0GHz/(mA)0.5 and a -factor of 0.41 ns are measured.EC/FP7/224211/EU/VISIT - Vertically Integrated Systems for Information Transfer/VISITDFG, 43659573, SFB 787: Halbleiter - Nanophotonik: Materialien, Modelle, Bauelement
Single-drive high-speed lumped depletion-type modulators toward 10 fJ/bit energy consumption
No full textReduction of modulator energy consumption to 10 fJ/bit is essential for the sustainable development of communication systems. Lumped modulators might be a viable solution if instructed by a complete theory system. Here, we present a complete analytical electro-optic response theory, energy consumption analysis, and eye diagrams on absolute scales for lumped modulators. Consequently the speed limitation is understood and alleviated by single-drive configuration, and comprehensive knowledge into the energy dependence on structural parameters significantly reduces energy consumption. The results show that silicon modulation energy as low as 80.8 and 21.5 fJ/bit can be achieved at 28 Gbd under 50 and 10 Omega impedance drivers, respectively. A 50 Gbd modulation is also shown to be possible. The analytical models can be extended to lumped modulators on other material platforms and offer a promising solution to the current challenges of modulation energy reduction. (C) 2017 Chinese Laser PressNational Natural Science Foundation of China (NSFC) [61120106012]SCI(E)ARTICLE2134-142
Elacytarabine has single-agent activity in patients with advanced acute myeloid leukaemia
No full textUnexpected high incidence of severe toxicities associated with alpha interferon, low-dose cytosine arabinoside and all-trans retinoic acid in patients with chronic myelogenous leukemia. Leuk Lymphoma.
No full textPreclinical data have shown that all-trans retinoic acid (ATRA) with interferon-alpha (IFN-alpha) can exert significant suppressive effects on Philadelphia-chromosome (Ph)-positive cells. The aim of this study combining IFN-alpha, low-dose cytosine arabinoside (ara-C) and ATRA was to increase the proportion of patients achieving a major cytogenetic response, in comparison with a group of 140 patients previously treated with IFN-alpha plus low-dose ara-C. Forty three patients with Ph-positive CML in early chronic phase were treated with IFN-alpha 5 MU/m2 s.c. daily, low-dose ara-C 10 mg s.c. daily and ATRA 45 mg/m2 orally daily, for 7 consecutive days every other week. Overall, 76% of patients achieved a complete hematologic response (CHR). A cytogenetic response was in observed 59% (major in 38% and complete in 17%). Compared with patients treated with IFN-alpha and low-dose ara-C, those receiving additional ATRA had a lower CHR rate (p. 014), but other response rates were similar. Severe toxicities were common with the triple regimen (64%), mostly related to ATRA therapy. Two patients experienced pseudotumor cerebri; two patients had leukocytosis during the week on ATRA treatment, decreasing during the week off (one suffered a severe asthma-like reaction followed by pulmonary edema, resembling ATRA syndrome). Six patients had other unusual side-effects: aseptic necrosis of the hip (1 patient), ataxic syndrome (1 patient), paranoid syndrome (2 patients), syncopal episodes (1 patient), pure red cell aplasia (1 patient). In conclusion the results of IFN-alpha and low-dose ara-C combined with ATRA in patients with early CML-chronic phase were disappointing, due to excessive toxicity. Whether different ATRA dose schedules may result in fewer side-effects and improve hematologic and cytogenetic response remains to be determined
Nilotinib is effective in patients with chronic myeloid leukemia in chronic phase after imatinib resistance or intolerance: 24-month follow-up results
No full textNilotinib is a potent selective inhibitor of the BCR-ABL tyrosine kinase approved for use in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CMLCP), and in CML-CP and CML-accelerated phase after imatinib failure. Nilotinib (400 mg twice daily) was approved on the basis of the initial results of this phase 2 open-label study. The primary study endpoint was the proportion of patients achieving major cytogenetic response (CyR). All patients were followed for > 24 months or discontinued early. Of 321 patients, 124 (39%) continue on nilotinib treatment. Overall, 59% of patients achieved major CyR; this was completeCyR(CCyR) in 44%. Of patients achieving CCyR,56% achieved major molecular response. CyRs were durable, with 84% of patients who achieved CCyR maintaining response at 24 months. The overall survival at 24 months was 87%. Adverse events were mostly mild to moderate, generally transient, and easily managed. This study indicates that nilotinib is effective, with a manageable safety profile, and can provide favorable long-term benefits for patients with CML-CP after imatinib failure. This trial was registered at www.clinicaltrials.gov as #NCT00109707.Hagop M. Kantarjian, Francis J. Giles, Kapil N. Bhalla, Javier Pinilla-Ibarz,Richard A. Larson, Norbert Gattermann, Oliver G. Ottmann, Andreas Hochhaus, Giuseppe Saglio, Timothy P. Hughes, Giovanni Martinelli, Dong-Wook Kim, Yaping Shou, Neil J. Gallagher, Rick Blakesley, Michele Baccarani, Jorge Cortes and Philipp D. le Coutr
Dispersal and remineralisation of biodeposits: Ecosystem impacts of mussel aquaculture
No full textSuspension-feeding bivalves produce biodeposits (faeces and pseudofaeces) that have much higher sinking velocities than their constituent particles. Consequently they cause sedimentation of material that might otherwise not be deposited. The benthic remineralisation of biodeposits increases sediment oxygen demand and nutrient regeneration, thus enhancing the benthic-pelagic coupling of nearshore ecosystems. In New Zealand the mussel Perna canaliculus has a high natural abundance and is also intensively cultured. This thesis examines the dispersal and remineralisation characteristics of mussel P. canaliculus biodeposits and the impacts of sedimentation from a mussel farm in the Firth of Thames on sediment biogeochemistry by combining laboratory, field and modelling studies.
Dispersal characteristics were examined in the laboratory by measuring sinking velocities and erosion thresholds of biodeposits produced by mussels of a wide size range fed three experimental diets. The results show that biodeposit dispersal is a function of mussel diet and size and thus could differ significantly between locations and seasons. Estimates of dispersal distances based on these results demonstrated that the initial dispersal of biodeposits produced by cultured mussels is not far. Depending on the hydrodynamic conditions, secondary dispersal via resuspension potentially plays a more important role in the dispersal of biodeposits from mussel farms than initial dispersal and almost certainly serves as the major means of transport of biodeposits from natural mussel beds.
Biodeposit mineralisation was studied by incubating coastal sediments with added biodeposits and measuring oxygen and nutrient fluxes as well as sediment characteristics over an 11 d period. Sediment oxygen consumption and ammonium release increased immediately after biodeposit addition and remained elevated compared to control cores without additions for the incubation period. A biodeposit decay rate (0.16 d-1) was calculated by fitting a first-order G model to the observed increase in oxygen consumption. This rate is 1 - 2 orders of magnitude higher than published decay rates of coastal sediments without organic enrichment or plant material. Nutrient fluxes during the incubation period illustrated that biodeposit remineralisation alters the stoichiometry of the nutrients released from the sediments which may potentially be more significant than the changes of the individual fluxes.
To determine the impact of a mussel farm in the Firth of Thames I measured sediment oxygen and nutrient fluxes by deploying benthic chambers, sediment characteristics by collecting sediment cores and sedimentation rates by deploying sediment traps in four seasons. Oxygen consumption and sediment nutrient release rates were generally higher under the farm compared to a reference site, demonstrating the typical response to increased organic input. Unusually low nitrogen release rates measured in summer may indicate enhanced denitrification under the farm. A simple budget demonstrated the importance of benthic nutrient regeneration in maintaining primary production in this region and that mussel culture can lead to a redistribution of nutrients. This study showed that site-specific hydrodynamic and biogeochemical conditions have to be taken into account when planning new mussel farms to prevent excessive modifications of nutrient dynamics.
Results of the laboratory and field studies conducted in this thesis were used to parameterise, calibrate and validate models of mussel biodeposit dispersal and remineralisation. A particle tracking model showed that the maximum initial dispersal of faecal pellets from the mussel farm is approximately 300 m and that pellets can be transported several times this distance via resuspension. The remineralisation model was able to simulate the increased nitrogen fluxes from the sediments well and highlighted the need for thorough calibration and parameterisation of the model.
This thesis contributed to the current understanding of the ecosystem impacts of mussel culture and provided numerical models and model parameters that will assist in the assessment of mussel culture sustainability and the contribution of mussels to the nutrient cycling in nearshore ecosystems
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