462 research outputs found
PCV130 PRACTICE PATTERNS AND QUALITY OF LIFE IN ACUTE CORONARY SYNDROME PATIENTS IN 2008–2009: BASELINE RESULTS FOR AUSTRIA FROM THE ANTIPLATELET TREATMENT OBSERVATIONAL REGISTRY II (APTOR II)
PCV26 PRACTICE PATTERNS AND QUALITY OF LIFE IN PATIENTS WITH ACUTE CORONARY SYNDROME IN THE NORDIC COUNTRIES: RESULTS FROM THE ANTIPLATELET TREATMENT OBSERVATIONAL REGISTRY II (APTOR II)
Land surface phenological response to decadal climate variability across Australia using satellite remote sensing
© 2014 Author(s). Land surface phenological cycles of vegetation greening and browning are influenced by variability in climatic forcing. Quantitative spatial information on phenological cycles and their variability is important for agricultural applications, wildfire fuel accumulation, land management, land surface modeling, and climate change studies. Most phenology studies have focused on temperature-driven Northern Hemisphere systems, where phenology shows annually recurring patterns. However, precipitation-driven non-annual phenology of arid and semi-arid systems (i.e., drylands) received much less attention, despite the fact that they cover more than 30% of the global land surface. Here, we focused on Australia, a continent with one of the most variable rainfall climates in the world and vast areas of dryland systems, where a detailed phenological investigation and a characterization of the relationship between phenology and climate variability are missing. To fill this knowledge gap, we developed an algorithm to characterize phenological cycles, and analyzed geographic and climate-driven variability in phenology from 2000 to 2013, which included extreme drought and wet years. We linked derived phenological metrics to rainfall and the Southern Oscillation Index (SOI). We conducted a continent-wide investigation and a more detailed investigation over the Murray-Darling Basin (MDB), the primary agricultural area and largest river catchment of Australia. Results showed high inter-and intra-annual variability in phenological cycles across Australia. The peak of phenological cycles occurred not only during the austral summer, but also at any time of the year, and their timing varied by more than a month in the interior of the continent. The magnitude of the phenological cycle peak and the integrated greenness were most significantly correlated with monthly SOI within the preceding 12 months. Correlation patterns occurred primarily over northeastern Australia and within the MDB, predominantly over natural land cover and particularly in floodplain and wetland areas. Integrated greenness of the phenological cycles (surrogate of vegetation productivity) showed positive anomalies of more than 2 standard deviations over most of eastern Australia in 2009-2010, which coincided with the transition from the El Niño-induced decadal droughts to flooding caused by La Niña
Universal quantum control of two-electron spin quantum bits using dynamic nuclear polarization
One fundamental requirement for quantum computation is to perform universal
manipulations of quantum bits at rates much faster than the qubit's rate of
decoherence. Recently, fast gate operations have been demonstrated in logical
spin qubits composed of two electron spins where the rapid exchange of the two
electrons permits electrically controllable rotations around one axis of the
qubit. However, universal control of the qubit requires arbitrary rotations
around at least two axes. Here we show that by subjecting each electron spin to
a magnetic field of different magnitude we achieve full quantum control of the
two-electron logical spin qubit with nanosecond operation times. Using a single
device, a magnetic field gradient of several hundred milliTesla is generated
and sustained using dynamic nuclear polarization of the underlying Ga and As
nuclei. Universal control of the two-electron qubit is then demonstrated using
quantum state tomography. The presented technique provides the basis for single
and potentially multiple qubit operations with gate times that approach the
threshold required for quantum error correction.Comment: 11 pages, 4 figures. Supplementary Material included as ancillary
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Molecular alterations that drive breast cancer metastasis to bone.
Epithelial cancers including breast and prostate commonly progress to form incurable bone metastases. For this to occur, cancer cells must adapt their phenotype and behaviour to enable detachment from the primary tumour, invasion into the vasculature, and homing to and subsequent colonisation of bone. It is widely accepted that the metastatic process is driven by the transformation of cancer cells from a sessile epithelial to a motile mesenchymal phenotype through epithelial-mesenchymal transition (EMT). Dissemination of these motile cells into the circulation provides the conduit for cells to metastasise to distant organs. However, accumulating evidence suggests that EMT is not sufficient for metastasis to occur and that specific tissue-homing factors are required for tumour cells to lodge and grow in bone. Once tumour cells are disseminated in the bone environment, they can revert into an epithelial phenotype through the reverse process of mesenchymal-epithelial transition (MET) and form secondary tumours. In this review, we describe the molecular alterations undertaken by breast cancer cells at each stage of the metastatic cascade and discuss how these changes facilitate bone metastasis
Resistance to HER2-targeted therapies in HER2-positive breast cancer
Breast cancer accounts for 522,000 deaths worldwide each year and is the most common
cancer in women. It is classified according to the cell of origin and its expression of
several receptors: oestrogen and progesterone receptors, and human epidermal growth
factor receptor 2 (HER2).
Historically, HER2-positive breast cancers had a worse survival prognosis than oestrogen
or progesterone receptor-positive cancers, but the development of HER2-targeted
therapies led to significant survival improvements. Despite this, patients often present
with de novo resistance, or will develop acquired resistance to targeted therapies.
Several resistance mechanisms have been identified but attempts to target them have
failed. Thus, it is of paramount importance to identify the mechanisms used, to prevent
development of resistance or resensitise tumours to HER2-targeted therapies. Objectives
of this study were: to understand the link between epithelial to mesenchymal transition
(EMT) and loss of HER2, seen in a model of acquired resistance to the HER2-targeted
therapy, sapatinib, and to characterise and validate tumours from a sapatinib-treated
spontaneous mouse model of HER2-positive breast cancer.
The EMT-linked transcription factor ZEB1 was associated with acquired resistance to
sapatinib in tumours that had undergone EMT and concurrently lost HER2. Generation
of drug resistant cell lines failed to recapitulate the in vivo phenotype. Transient
overexpression of ZEB1 in vitro did not induce clear EMT or loss of HER2, despite
a trend towards lower HER2 expression. However, we found that treatment of cells
with ERBB2 shRNA, the gene encoding HER2, increased levels of ZEB1 and enhanced
migration, but did not induce overt EMT. This may be the result of differing PTEN
status between in vivo and in vitro models.
Treatment of a spontaneous mouse model of HER2-positive breast cancer with sapatinib
revealed that progressing tumours had an increase in proteins associated with cellular
iron homeostasis. Further investigation revealed increased heme oxygenase-1 (HO-1),
iron exporter ferroportin and altered iron storage.
To ascertain if modulation of dietary iron intake could affect the development of resistance
to sapatinib, mice were given a control or iron-deficient diet and treated with vehicle or
sapatinib. This showed that in sapatinib-treated mice fed an iron-deficient diet, HO-1
was not increased as in tumours from mice fed a iron-low control diet.
We looked at the possibility of HER2-targeting therapies inducing ferroptosis, an iron-dependent
form of cell death. Sapatinib-treated tumours from mice on a iron-low control
diet had increased cyclooxygenase 2 (COX2), a marker of ferroptosis, which was not
seen in sapatinib-treated tumours from mice on an iron-deficient diet. Additionally, in
vitro drug treatments with HER2-targeting agents showed that SKBR3 cell death could
be rescued by iron chelation.
HO-1 overexpression in SKBR3 cells revealed increased autophagic flux and resistance to
HER2-targeted therapies. Inhibition of autophagy reversed resistance, rendering them
susceptible to sapatinib- and lapatinib-induced cell death. Further, increased autophagic
flux was seen in all progressive tumours on sapatinib. The increased resistance to
sapatinib in mice fed an iron-deficient diet was also associated with increased autophagic
flux, although this was HO-1-independent.
Taken together, the results presented here provide a novel mechanism of cell death
induced by HER2-targeting agents in vitro and in vivo. We have shown that increased
HO-1 and reducing dietary iron can affect the development of resistance to sapatinib,
which is reliant on autophagy induction. Further, inhibiting autophagy can resensitise
cells to sapatinib and lapatinib treatment
Women We Loved: Paradoxes of public and private in the biographical television drama
Broadcast to critical acclaim and relatively large audiences for its niche channel, the Women We Loved season consisted of biographical dramatisations of three prominent female figures of 20th-century British culture. These dramas shared in common narratives that centre on the two aspects of ‘the public’ and ‘the private’: the tension between public career and personal life and the discrepancy between celebrity persona and private individual. Combining theoretical insights from feminist studies of biography with close textual analysis, this article analyses how performance, aesthetics and narrative express the ambivalent placement of their protagonists between public and private
spheres
The community impact of the 2009 influenza pandemic in the WHO European Region: a comparison with historical seasonal data from 28 countries
Contains fulltext :
109779.pdf (publisher's version ) (Open Access)BACKGROUND: The world has recently experienced the first influenza pandemic of the 21st century that lasted 14 months from June 2009 to August 2010. This study aimed to compare the timing, geographic spread and community impact during the winter wave of influenza pandemic A (H1N1) 2009 to historical influenza seasons in countries of the WHO European region. METHODS: We assessed the timing of pandemic by comparing the median peak of influenza activity in countries of the region during the last seven influenza seasons. The peaks of influenza activity were selected by two independent researchers using predefined rules. The geographic spread was assessed by correlating the peak week of influenza activity in included countries against the longitude and latitude of the central point in each country. To assess the community impact of pandemic influenza, we constructed linear regression models to compare the total and age-specific influenza-like-illness (ILI) or acute respiratory infection (ARI) rates reported by the countries in the pandemic season to those observed in the previous six influenza seasons. RESULTS: We found that the influenza activity reached its peak during the pandemic, on average, 10.5 weeks (95% CI 6.4-14.2) earlier than during the previous 6 seasons in the Region, and there was a west to east spread of pandemic A(H1N1) influenza virus in the western part of the Region. A regression analysis showed that the total ILI or ARI rates were not higher than historical rates in 19 of the 28 countries. However, in countries with age-specific data, there were significantly higher consultation rates in the 0-4 and/or 5-14 age groups in 11 of the 20 countries. CONCLUSIONS: Using routine influenza surveillance data, we found that pandemic influenza had several differential features compared to historical seasons in the region. It arrived earlier, caused significantly higher number of outpatient consultations in children in most countries and followed west to east spread that was previously observed during some influenza seasons with dominant A (H3N2) ifluenza viruses. The results of this study help to understand the epidemiology of 2009 influenza pandemic and can be used for pandemic preparedness planning
Chlamydia trachomatis prevalence in undocumented migrants undergoing voluntary termination of pregnancy: a prospective cohort study
BACKGROUND: Chlamydia trachomatis infection (CTI) is the most frequent sexual transmitted disease (STI) in Switzerland but its prevalence in undocumented migrants is unknown. We aimed to compare CTI prevalence among undocumented migrants undergoing termination of pregnancy (ToP) to the prevalence among women with residency permit. METHODS: This prospective cohort study included all pregnant, undocumented women presenting from March 2005 to October 2006 to the University hospital for ToP. The control group consisted of a systematic sample of pregnant women with legal residency permit coming to the same hospital during the same time period for ToP. RESULTS: One hundred seventy five undocumented women and 208 women with residency permit (controls) were included in the study. Mean ages were 28.0 y (SD 5.5) and 28.2 y (SD 7.5), respectively (p = 0.77). Undocumented women came primarily from Latin-America (78%). Frequently, they lacked contraception (23%, controls 15%, OR 1.8, 95% CI 1.04;2.9). Thirteen percent of undocumented migrants were found to have CTI (compared to 4.4% of controls; OR 3.2, 95% CI 1.4;7.3). CONCLUSION: This population of undocumented, pregnant migrants consisted primarily of young, Latino-American women. Compared to control women, undocumented migrants showed higher prevalence rates of genital CTI, which indicates that health professionals should consider systematic screening for STI in this population. There is a need to design programs providing better access to treatment and education and to increase migrants' awareness of the importance of contraception and transmission of STI
Rapid Detection and Subtyping of Human Influenza A Viruses and Reassortants by Pyrosequencing
Background: Given the continuing co-circulation of the 2009 H1N1 pandemic influenza A viruses with seasonal H3N2 viruses, rapid and reliable detection of newly emerging influenza reassortant viruses is important to enhance our influenza surveillance. Methodology/Principal Findings: A novel pyrosequencing assay was developed for the rapid identification and subtyping of potential human influenza A virus reassortants based on all eight gene segments of the virus. Except for HA and NA genes, one universal set of primers was used to amplify and subtype each of the six internal genes. With this method, all eight gene segments of 57 laboratory isolates and 17 original specimens of seasonal H1N1, H3N2 and 2009 H1N1 pandemic viruses were correctly matched with their corresponding subtypes. In addition, this method was shown to be capable of detecting reassortant viruses by correctly identifying the source of all 8 gene segments from three vaccine production reassortant viruses and three H1N2 viruses. Conclusions/Significance: In summary, this pyrosequencing assay is a sensitive and specific procedure for screening large numbers of viruses for reassortment events amongst the commonly circulating human influenza A viruses, which is mor
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