Central nervous system relapse in patients with breast cancer is associated with advanced stages, with the presence of circulating occult tumor cells and with the HER2/neu status

INTRODUCTION: To evaluate the incidence of central nervous system (CNS) involvement in patients with breast cancer treated with a taxane-based chemotherapy regimen and to determine predictive factors for CNS relapse. METHODS: The medical files of patients with early breast cancer (n = 253) or advanced stage breast cancer (n = 239) as well of those with other solid tumors (n = 336) treated with or without a taxane-based chemotherapy regimen during a 42-month period were reviewed. HER2/neu overexpression was identified by immunohistochemistry, whereas cytokeratin 19 (CK-19) mRNA-positive circulating tumor cells (CTCs) in the peripheral blood were identified by real-time PCR. RESULTS: The incidence of CNS relapse was similar in patients suffering from breast cancer or other solid tumors (10.4% and 11.4%, respectively; P = 0.517). The incidence of CNS relapse was significantly higher in breast cancer patients with advanced disease (P = 0.041), visceral disease and bone disease (P = 0.036), in those who were treated with a taxane-containing regimen (P = 0.024), in those with HER2/neu-overexpressing tumors (P = 0.022) and, finally, in those with detectable CK-19 mRNA-positive CTCs (P = 0.008). Multivariate analysis revealed that the stage of disease (odds ratio, 0.23; 95% confidence interval, 0.007–0.23; P = 0.0001), the HER2/neu status (odds ratio, 29.4; 95% confidence interval, 7.51–101.21; P = 0.0001) and the presence of CK-19 mRNA-positive CTCs (odds ratio, 8.31; 95% confidence interval, 3.97–12.84; P = 0.001) were independent predictive factors for CNS relapse. CONCLUSION: CNS relapses are common among breast cancer patients treated with a taxane-based chemotherapy regimen, patients with HER2/neu-positive tumor and patients with CK-19 mRNA-positive CTCs

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

The p53 Tumor Suppressor-Like Protein nvp63 Mediates Selective Germ Cell Death in the Sea Anemone Nematostella vectensis

Here we report the identification and molecular function of the p53 tumor suppressor-like protein nvp63 in a non-bilaterian animal, the starlet sea anemone Nematostella vectensis. So far, p53-like proteins had been found in bilaterians only. The evolutionary origin of p53-like proteins is highly disputed and primordial p53-like proteins are variably thought to protect somatic cells from genotoxic stress. Here we show that ultraviolet (UV) irradiation at low levels selectively induces programmed cell death in early gametes but not somatic cells of adult N. vectensis polyps. We demonstrate with RNA interference that nvp63 mediates this cell death in vivo. Nvp63 is the most archaic member of three p53-like proteins found in N. vectensis and in congruence with all known p53-like proteins, nvp63 binds to the vertebrate p53 DNA recognition sequence and activates target gene transcription in vitro. A transactivation inhibitory domain at its C-terminus with high homology to the vertebrate p63 may regulate nvp63 on a molecular level. The genotoxic stress induced and nvp63 mediated apoptosis in N. vectensis gametes reveals an evolutionary ancient germ cell protective pathway which relies on p63-like proteins and is conserved from cnidarians to vertebrates

Water Contamination Reduces the Tolerance of Coral Larvae to Thermal Stress

Coral reefs are highly susceptible to climate change, with elevated sea surface temperatures (SST) posing one of the main threats to coral survival. Successful recruitment of new colonies is important for the recovery of degraded reefs following mortality events. Coral larvae require relatively uncontaminated substratum on which to metamorphose into sessile polyps, and the increasing pollution of coastal waters therefore constitutes an additional threat to reef resilience. Here we develop and analyse a model of larval metamorphosis success for two common coral species to quantify the interactive effects of water pollution (copper contamination) and SST. We identify thresholds of temperature and pollution that prevent larval metamorphosis, and evaluate synergistic interactions between these stressors. Our analyses show that halving the concentration of Cu can protect corals from the negative effects of a 2–3°C increase in SST. These results demonstrate that effective mitigation of local impacts can reduce negative effects of global stressors

Impacts of Sediments on Coral Energetics: Partitioning the Effects of Turbidity and Settling Particles

Sediment loads have long been known to be deleterious to corals, but the effects of turbidity and settling particles have not previously been partitioned. This study provides a novel approach using inert silicon carbide powder to partition and quantify the mechanical effects of sediment settling versus reduced light under a chronically high sedimentary regime on two turbid water corals commonly found in Singapore (Galaxea fascicularis and Goniopora somaliensis). Coral fragmentswere evenly distributed among three treatments: an open control (30% ambient PAR), a shaded control (15% ambient PAR) and sediment treatment (15% ambient PAR; 26.4 mg cm22 day21). The rate of photosynthesis and respiration, and the dark-adapted quantum yield were measured once a week for four weeks. By week four, the photosynthesis to respiration ratio (P/R ratio) and the photosynthetic yield (Fv/Fm) had fallen by 14% and 3–17% respectively in the shaded control,contrasting with corals exposed to sediments whose P/R ratio and yield had declined by 21% and 18–34% respectively. The differences in rates between the shaded control and the sediment treatment were attributed to the mechanical effects of sediment deposition. The physiological response to sediment stress differed between species with G. fascicularis experiencing a greater decline in the net photosynthetic yield (13%) than G. somaliensis (9.5%), but a smaller increase in the respiration rates (G. fascicularis = 9.9%, G. somaliensis = 14.2%). These different physiological responses were attributed, in part, to coral morphology and highlighted key physiological processes that drive species distribution along high to low turbidity and depositional gradients

Coral Uptake of Inorganic Phosphorus and Nitrogen Negatively Affected by Simultaneous Changes in Temperature and pH

The effects of ocean acidification and elevated seawater temperature on coral calcification and photosynthesis have been extensively investigated over the last two decades, whereas they are still unknown on nutrient uptake, despite their importance for coral energetics. We therefore studied the separate and combined impacts of increases in temperature and pCO2 on phosphate, ammonium, and nitrate uptake rates by the scleractinian coral S. pistillata. Three experiments were performed, during 10 days i) at three pHT conditions (8.1, 7.8, and 7.5) and normal temperature (26°C), ii) at three temperature conditions (26°, 29°C, and 33°C) and normal pHT (8.1), and iii) at three pHT conditions (8.1, 7.8, and 7.5) and elevated temperature (33°C). After 10 days of incubation, corals had not bleached, as protein, chlorophyll, and zooxanthellae contents were the same in all treatments. However, photosynthetic rates significantly decreased at 33°C, and were further reduced for the pHT 7.5. The photosynthetic efficiency of PSII was only decreased by elevated temperature. Nutrient uptake rates were not affected by a change in pH alone. Conversely, elevated temperature (33°C) alone induced an increase in phosphate uptake but a severe decrease in nitrate and ammonium uptake rates, even leading to a release of nitrogen into seawater. Combination of high temperature (33°C) and low pHT (7.5) resulted in a significant decrease in phosphate and nitrate uptake rates compared to control corals (26°C, pHT = 8.1). These results indicate that both inorganic nitrogen and phosphorus metabolism may be negatively affected by the cumulative effects of ocean warming and acidification

Evaluating Patterns of a White-Band Disease (WBD) Outbreak in Acropora palmata Using Spatial Analysis: A Comparison of Transect and Colony Clustering

. Likewise, there is little known about the spatiality of outbreaks. We examined the spatial patterns of WBD during a 2004 outbreak at Buck Island Reef National Monument in the US Virgin Islands. colonies with and without WBD.As the search for causation continues, surveillance and proper documentation of the spatial patterns may inform etiology, and at the same time assist reef managers in allocating resources to tracking the disease. Our results indicate that the spatial scale of data collected can drastically affect the calculation of prevalence and spatial distribution of WBD outbreaks. Specifically, we illustrate that higher resolution sampling resulted in more realistic disease estimates. This should assist in selecting appropriate sampling designs for future outbreak investigations. The spatial techniques used here can be used to facilitate other coral disease studies, as well as, improve reef conservation and management

Major Cellular and Physiological Impacts of Ocean Acidification on a Reef Building Coral

As atmospheric levels of CO2 increase, reef-building corals are under greater stress from both increased sea surface temperatures and declining sea water pH. To date, most studies have focused on either coral bleaching due to warming oceans or declining calcification due to decreasing oceanic carbonate ion concentrations. Here, through the use of physiology measurements and cDNA microarrays, we show that changes in pH and ocean chemistry consistent with two scenarios put forward by the Intergovernmental Panel on Climate Change (IPCC) drive major changes in gene expression, respiration, photosynthesis and symbiosis of the coral, Acropora millepora, before affects on biomineralisation are apparent at the phenotype level. Under high CO2 conditions corals at the phenotype level lost over half their Symbiodinium populations, and had a decrease in both photosynthesis and respiration. Changes in gene expression were consistent with metabolic suppression, an increase in oxidative stress, apoptosis and symbiont loss. Other expression patterns demonstrate upregulation of membrane transporters, as well as the regulation of genes involved in membrane cytoskeletal interactions and cytoskeletal remodeling. These widespread changes in gene expression emphasize the need to expand future studies of ocean acidification to include a wider spectrum of cellular processes, many of which may occur before impacts on calcification

Effects of Trophic Skewing of Species Richness on Ecosystem Functioning in a Diverse Marine Community

Widespread overharvesting of top consumers of the world’s ecosystems has “skewed” food webs, in terms of biomass and species richness, towards a generally greater domination at lower trophic levels. This skewing is exacerbated in locations where exotic species are predominantly low-trophic level consumers such as benthic macrophytes, detritivores, and filter feeders. However, in some systems where numerous exotic predators have been added, sometimes purposefully as in many freshwater systems, food webs are skewed in the opposite direction toward consumer dominance. Little is known about how such modifications to food web topology, e.g., changes in the ratio of predator to prey species richness, affect ecosystem functioning. We experimentally measured the effects of trophic skew on production in an estuarine food web by manipulating ratios of species richness across three trophic levels in experimental mesocosms. After 24 days, increasing macroalgal richness promoted both plant biomass and grazer abundance, although the positive effect on plant biomass disappeared in the presence of grazers. The strongest trophic cascade on the experimentally stocked macroalgae emerged in communities with a greater ratio of prey to predator richness (bottom-rich food webs), while stronger cascades on the accumulation of naturally colonizing algae (primarily microalgae with some early successional macroalgae that recruited and grew in the mesocosms) generally emerged in communities with greater predator to prey richness (the more top-rich food webs). These results suggest that trophic skewing of species richness and overall changes in food web topology can influence marine community structure and food web dynamics in complex ways, emphasizing the need for multitrophic approaches to understand the consequences of marine extinctions and invasions